Viruses

19 pages, 3575 KiB

Open AccessArticle

Putting a Kink in HIV-1 Particle Infectivity: Rocaglamide Inhibits HIV-1 Replication by Altering Gag-Genomic RNA Interaction

by Paul Rosenfeld, Gatikrushna Singh, Amanda Paz Herrera, Juan Ji, Bradley Seufzer, Xiao Heng, Kathleen Boris-Lawrie and Alan Cochrane

Viruses 2024, 16(9), 1506; https://doi.org/10.3390/v16091506 - 23 Sep 2024

Viewed by 865

Abstract

Our examination of RNA helicases for effects on HIV-1 protein production and particle assembly identified Rocaglamide (RocA), a known modulator of eIF4A1 function, as an inhibitor of HIV-1 replication in primary CD4⁺ T cells and three cell systems. HIV-1 attenuation by low-nM [...] Read more.

Our examination of RNA helicases for effects on HIV-1 protein production and particle assembly identified Rocaglamide (RocA), a known modulator of eIF4A1 function, as an inhibitor of HIV-1 replication in primary CD4⁺ T cells and three cell systems. HIV-1 attenuation by low-nM RocA doses was associated with reduced viral particle formation without a marked decrease in Gag production. Rather, the co-localization of Gag and HIV-1 genomic RNA (gRNA) assemblies was impaired by RocA treatment in a reversible fashion. Ribonucleoprotein (RNP) immunoprecipitation studies recapitulated the loss of Gag-gRNA assemblies upon RocA treatment. Parallel biophysical studies determined that neither RocA nor eIF4A1 independently affected the ability of Gag to interact with viral RNA, but together, they distorted the structure of the HIV-1 RNP visualized by electron microscopy. Taken together, several lines of evidence indicate that RocA induces stable binding of eIF4A1 onto the viral RNA genome in a manner that interferes with the ordered assembly of Gag along Gag-gRNA assemblies required to generate infectious virions. Full article

(This article belongs to the Special Issue HIV Assembly, Release and Maturation)

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9 pages, 397 KiB

Open AccessArticle

Clinical Evaluation of the VirClia IgM/IgG Chemiluminescence Tests for the Diagnosis of Tick-Borne Encephalitis in an Endemic Part of Norway

by Åshild Marvik and Susanne Gjeruldsen Dudman

Viruses 2024, 16(9), 1505; https://doi.org/10.3390/v16091505 - 23 Sep 2024

Viewed by 721

Abstract

The aim of this study was to evaluate the clinical usefulness of VirClia IgM/IgG single-assay chemiluminescence tests for the diagnosis of tick-borne encephalitis (TBE) in an endemic part of Norway. Patients hospitalized at Vestfold or Telemark Hospitals with suspected infection in the central [...] Read more.

The aim of this study was to evaluate the clinical usefulness of VirClia IgM/IgG single-assay chemiluminescence tests for the diagnosis of tick-borne encephalitis (TBE) in an endemic part of Norway. Patients hospitalized at Vestfold or Telemark Hospitals with suspected infection in the central nervous system (CNS) in the period between May 2021 and December 2023 were included, with 85 TBE cases identified. The VirClia IgM assay was positive in the initial serum sample in 75/85 cases, giving a sensitivity of 88.2% (95% CI, 79.4–94.2). The ReaScan TBE IgM rapid test was positive in 80/85 cases, with an estimated sensitivity of 94.1% (95% CI, 86.8–98.1). Vaccine breakthrough infections were the predominant cause of non-reactive IgM cases. The calculated specificity for the VirClia IgM was 95.8% (95% CI, 92.5–98.0). In conclusion, the sensitivity of the VirClia IgM was non-inferior to the ReaScan TBE IgM rapid test. However, isolated IgM reactive results must be interpreted with caution, since false-reactive results occur. Full article

(This article belongs to the Special Issue Tick-Borne Viruses: Transmission and Surveillance)

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13 pages, 3324 KiB

Open AccessReview

Zooming in and out: Exploring RNA Viral Infections with Multiscale Microscopic Methods

by Cheng-An Lyu, Yao Shen and Peijun Zhang

Viruses 2024, 16(9), 1504; https://doi.org/10.3390/v16091504 - 23 Sep 2024

Viewed by 848

Abstract

RNA viruses, being submicroscopic organisms, have intriguing biological makeups and substantially impact human health. Microscopic methods have been utilized for studying RNA viruses at a variety of scales. In order of observation scale from large to small, fluorescence microscopy, cryo-soft X-ray tomography (cryo-SXT), [...] Read more.

RNA viruses, being submicroscopic organisms, have intriguing biological makeups and substantially impact human health. Microscopic methods have been utilized for studying RNA viruses at a variety of scales. In order of observation scale from large to small, fluorescence microscopy, cryo-soft X-ray tomography (cryo-SXT), serial cryo-focused ion beam/scanning electron microscopy (cryo-FIB/SEM) volume imaging, cryo-electron tomography (cryo-ET), and cryo-electron microscopy (cryo-EM) single-particle analysis (SPA) have been employed, enabling researchers to explore the intricate world of RNA viruses, their ultrastructure, dynamics, and interactions with host cells. These methods evolve to be combined to achieve a wide resolution range from atomic to sub-nano resolutions, making correlative microscopy an emerging trend. The developments in microscopic methods provide multi-fold and spatial information, advancing our understanding of viral infections and providing critical tools for developing novel antiviral strategies and rapid responses to emerging viral threats. Full article

(This article belongs to the Special Issue Microscopy Methods for Virus Research)

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19 pages, 8954 KiB

Open AccessArticle

N-Acetylcysteine Inhibits Coxsackievirus B3 Replication by Downregulating Eukaryotic Translation Elongation Factor 1 Alpha 1

by Yao Wang, Tian Luan, Lixin Wang, Danxiang Feng, Yanyan Dong, Siwei Li, Hong Yang, Yang Chen, Yanru Fei, Lexun Lin, Jiahui Pan, Zhaohua Zhong and Wenran Zhao

Viruses 2024, 16(9), 1503; https://doi.org/10.3390/v16091503 - 23 Sep 2024

Viewed by 980

Abstract

Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice [...] Read more.

Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice for several decades to treat various medical conditions. In this study, the anti-CVB effect of NAC was investigated. We show that NAC dramatically suppressed viral replication and alleviated cardiac injury induced by CVB3. To further study the antiviral mechanism of NAC, RNA-sequencing was performed for CVB3-infected cells with NAC treatment. We found that eukaryotic elongation factor 1 alpha 1 (EEF1A1) is one of the most upregulated genes in CVB3-infected cells. However, EEF1A2, the highly homologous isoform of EEF1A1, remains unchanged. EEF1A1 expression was significantly suppressed by NAC treatment in CVB3-infected cells, while EEF1A2 was not affected. eEF1A1 knockdown significantly inhibited CVB3 replication, implicating that eEF1A1 facilitates viral replication. Importantly, we show that eEF1A1, which was not expressed in the myocardia of newborn mice, was significantly upregulated by CVB3 infection. NAC markedly downregulated the expression of eEF1A1 but not eEF1A2 in the myocardia of CVB3-infected mice. Furthermore, NAC accelerated eEF1A1 degradation by promoting autophagy in CVB3-infected cells. We show that p62, one of the critical adaptors of autophagic targets, interacts with eEF1A1 and was downregulated in CVB3-infected cells upon NAC treatment. Taken together, this study demonstrated that NAC shows a potent anti-CVB effect through the downregulation of eEF1A1. Full article

(This article belongs to the Special Issue Innovative Drug Discovery for Emerging Viral Diseases)

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14 pages, 4449 KiB

Open AccessBrief Report

Evaluation of the Deletion of African Swine Fever Virus E111R Gene from the Georgia Isolate in Virus Replication and Virulence in Domestic Pigs

by Elizabeth Ramirez-Medina, Lauro Velazquez-Salinas, Alyssa Valladares, Amanda Meyers, Leeanna Burton, Ediane Silva, Jason Clark, Manuel V. Borca and Douglas P. Gladue

Viruses 2024, 16(9), 1502; https://doi.org/10.3390/v16091502 - 23 Sep 2024

Viewed by 677

Abstract

African swine fever virus (ASFV) is the causative agent of an often lethal disease in domestic pigs, African swine fever (ASF). ASF is currently a pandemic disease challenging pig production in Eurasia. While the ASFV genome encodes for over 160 proteins, the function [...] Read more.

African swine fever virus (ASFV) is the causative agent of an often lethal disease in domestic pigs, African swine fever (ASF). ASF is currently a pandemic disease challenging pig production in Eurasia. While the ASFV genome encodes for over 160 proteins, the function of most of them are still not characterized. Among those ASF genes with unknown functions is the E111R gene. It has been recently reported that the deletion of the E111R gene from the genome of the virulent Chinese field isolate SY18 strain produced a reduction of virus virulence when pigs were inoculated at relatively low doses. Conversely, we report here that deletion of the ASFV gene E111R in the Georgia 2010 isolate does not alter the virulence of the parental virus in experimentally inoculated pigs. A recombinant virus lacking the E111R gene, ASFV-G-∆E111R was intramuscularly (IM) inoculated in domestic pigs at a dose of 10² HAD₅₀ of ASFV-G-∆E111R and compared with animals that received a similar dose of virulent ASFV-G. Both, animals inoculated with either the recombinant ASFV-G-∆E111R or the parental virus developed a fatal form of the disease and were euthanized around the 6th–7th day post-inoculation (dpi). Full article

(This article belongs to the Special Issue African Swine Fever Virus 4.0)

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11 pages, 8056 KiB

Open AccessArticle

Evaluating the Use of Sacran, a Polysaccharide Isolated from Aphanothece sacrum, as a Possible Microbicide for Preventing HIV-1 Infection

by Kouki Matsuda, Ryusho Kariya, Kenji Maeda and Seiji Okada

Viruses 2024, 16(9), 1501; https://doi.org/10.3390/v16091501 - 23 Sep 2024

Viewed by 675

Abstract

Since combination antiretroviral therapy (cART) was introduced to treat human immunodeficiency virus type-1 (HIV-1)/acquired immunodeficiency syndrome (AIDS), the AIDS mortality rate has markedly decreased, and convalescence in individuals with HIV has improved drastically. However, sexual transmission has made HIV-1 a global epidemic. Sacran [...] Read more.

Since combination antiretroviral therapy (cART) was introduced to treat human immunodeficiency virus type-1 (HIV-1)/acquired immunodeficiency syndrome (AIDS), the AIDS mortality rate has markedly decreased, and convalescence in individuals with HIV has improved drastically. However, sexual transmission has made HIV-1 a global epidemic. Sacran is a megamolecular polysaccharide extracted from cyanobacterium Aphanothece sacrum that exhibits numerous desirable characteristics for transdermic applications, such as safety as a biomaterial, a high moisture retention effect, the ability to form a film and hydrogel, and an anti-inflammatory effect. In this study, we evaluated the anti-HIV-1 effects in sacran as a barrier to HIV-1 transmission. Sacran inhibited HIV-1 infection and envelope-dependent cell-to-cell fusion. Moreover, we used a Transwell assay to confirm that sacran inhibited viral diffusion and captured viruses. The synergistic effects of sacran and other anti-HIV infection drugs were also evaluated. HIV-1 infections can be reduced through the synergistic effects of sacran and anti-HIV-1 drugs. Our study suggests using sacran gel to provide protection against HIV-1 transmission. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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17 pages, 299 KiB

Open AccessArticle

The Omicron Variant Is Associated with a Reduced Risk of the Post COVID-19 Condition and Its Main Phenotypes Compared to the Wild-Type Virus: Results from the EuCARE-POSTCOVID-19 Study

by Francesca Bai, Andrea Santoro, Pontus Hedberg, Alessandro Tavelli, Sara De Benedittis, Júlia Fonseca de Morais Caporali, Carolina Coimbra Marinho, Arnaldo Santos Leite, Maria Mercedes Santoro, Francesca Ceccherini Silberstein, Marco Iannetta, Dovilé Juozapaité, Edita Strumiliene, André Almeida, Cristina Toscano, Jesús Arturo Ruiz-Quiñones, Chiara Mommo, Iuri Fanti, Francesca Incardona, Alessandro Cozzi-Lepri and Giulia Marchetti Show full author list Hide full author list

Viruses 2024, 16(9), 1500; https://doi.org/10.3390/v16091500 - 23 Sep 2024

Viewed by 1330

Abstract

Post COVID-19 condition (PCC) is defined as ongoing symptoms at ≥1 month after acute COVID-19. We investigated the risk of PCC in an international cohort according to viral variants. We included 7699 hospitalized patients in six centers (January 2020–June 2023); a subset of [...] Read more.

Post COVID-19 condition (PCC) is defined as ongoing symptoms at ≥1 month after acute COVID-19. We investigated the risk of PCC in an international cohort according to viral variants. We included 7699 hospitalized patients in six centers (January 2020–June 2023); a subset of participants with ≥1 visit over the year after clinical recovery were analyzed. Variants were observed or estimated using Global Data Science Initiative (GISAID) data. Because patients returning for a post COVID-19 visit may have a higher PCC risk, and because the variant could be associated with the probability of returning, we used weighted logistic regressions. We estimated the proportion of the effect of wild-type (WT) virus vs. Omicron on PCC, which was mediated by Intensive Care Unit (ICU) admission, through a mediation analysis. In total, 1317 patients returned for a post COVID visit at a median of 2.6 (IQR 1.84–3.97) months after clinical recovery. WT was present in 69.6% of participants, followed by the Alpha (14.4%), Delta (8.9%), Gamma (3.9%) and Omicron strains (3.3%). Among patients with PCC, the most common manifestations were fatigue (51.7%), brain fog (32.7%) and respiratory symptoms (37.2%). Omicron vs. WT was associated with a reduced risk of PCC and PCC clusters; conversely, we observed a higher risk with the Delta and Alpha variants vs. WT. In total, 42% of the WT effect vs. Omicron on PCC risk appeared to be mediated by ICU admission. A reduced PCC risk was observed after Omicron infection, suggesting a possible reduction in the PCC burden over time. A non-negligible proportion of the variant effect on PCC risk seems mediated by increased disease severity during the acute disease. Full article

(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae, 2nd Edition)

17 pages, 1660 KiB

Open AccessReview

Unleashing Nature’s Allies: Comparing the Vertical Transmission Dynamics of Insect-Specific and Vertebrate-Infecting Flaviviruses in Mosquitoes

by Alyssa J. Peterson, Roy A. Hall, Jessica J. Harrison, Jody Hobson-Peters and Leon E. Hugo

Viruses 2024, 16(9), 1499; https://doi.org/10.3390/v16091499 - 23 Sep 2024

Viewed by 1816

Abstract

Insect-specific viruses (ISVs) include viruses that are restricted to the infection of mosquitoes and are spread mostly through transovarial transmission. Despite using a distinct mode of transmission, ISVs are often phylogenetically related to arthropod-borne viruses (arboviruses) that are responsible for human diseases and [...] Read more.

Insect-specific viruses (ISVs) include viruses that are restricted to the infection of mosquitoes and are spread mostly through transovarial transmission. Despite using a distinct mode of transmission, ISVs are often phylogenetically related to arthropod-borne viruses (arboviruses) that are responsible for human diseases and able to infect both mosquitoes and vertebrates. ISVs can also induce a phenomenon called “superinfection exclusion”, whereby a primary ISV infection in an insect inhibits subsequent viral infections of the insect. This has sparked interest in the use of ISVs for the control of pathogenic arboviruses transmitted by mosquitoes. In particular, insect-specific flaviviruses (ISFs) have been shown to inhibit infection of vertebrate-infecting flaviviruses (VIFs) both in vitro and in vivo. This has shown potential as a new and ecologically friendly biological approach to the control of arboviral disease. For this intervention to have lasting impacts for biological control, it is imperative that ISFs are maintained in mosquito populations with high rates of vertical transmission. Therefore, these strategies will need to optimise vertical transmission of ISFs in order to establish persistently infected mosquito lines for sustainable arbovirus control. This review compares recent observations of vertical transmission of arboviral and insect-specific flaviviruses and potential determinants of transovarial transmission rates to understand how the vertical transmission of ISFs may be optimised for effective arboviral control. Full article

(This article belongs to the Special Issue Insect-Specific Viruses 2.0)

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42 pages, 11813 KiB

Open AccessSystematic Review

(Re-)Emergence of Oropouche Virus (OROV) Infections: Systematic Review and Meta-Analysis of Observational Studies

by Matteo Riccò, Silvia Corrado, Marco Bottazzoli, Federico Marchesi, Renata Gili, Francesco Paolo Bianchi, Emanuela Maria Frisicale, Stefano Guicciardi, Daniel Fiacchini, Silvio Tafuri, Antonio Cascio, Pasquale Gianluca Giuri and Roberta Siliquini

Viruses 2024, 16(9), 1498; https://doi.org/10.3390/v16091498 - 22 Sep 2024

Viewed by 2363

Abstract

Oropouche Virus (OROV; genus of Orthobunyavirus) is the causal agent of Oropouche Fever (OF). Due to the lack of specific signs and symptoms and the limited availability of diagnostic tests, the actual epidemiology of OROV infections and OF has been extensively disputed. In [...] Read more.

Oropouche Virus (OROV; genus of Orthobunyavirus) is the causal agent of Oropouche Fever (OF). Due to the lack of specific signs and symptoms and the limited availability of diagnostic tests, the actual epidemiology of OROV infections and OF has been extensively disputed. In this systematic review with meta-analysis, a literature search was carried out in PubMed, Scopus, EMBASE, and MedRxiv in order to retrieve relevant articles on the documented occurrence of OROV infections. Pooled detection rates were then calculated for anti-OROV antibodies and virus detection (i.e., viral RNA detected by viral cultures and/or real-time polymerase chain reaction [RT-qPCR]). Where available, detection rates for other arboviruses (i.e., Dengue [DENV], Chikungunya [CHKV], and Zika Virus [ZIKV]) were calculated and compared to those for OROV. A total of 47 studies from South America and the Caribbean were retrieved. In individuals affected by febrile illness during OROV outbreaks, a documented prevalence of 0.45% (95% confidence interval [95%CI] 0.16 to 1.12) for virus isolation, 12.21% (95%CI 4.96 to 27.09) for seroprevalence (including both IgM and IgG class antibodies), and 12.45% (95%CI 3.28 to 37.39) for the detection of OROV-targeting IgM class antibodies were eventually documented. In the general population, seroprevalence was estimated to be 24.45% (95%CI 7.83 to 55.21) for IgG class antibodies. The OROV detection rate from the cerebrospinal fluids of suspected cases of viral encephalitis was estimated to be 2.40% (95%CI 1.17 to 5.03). The occurrence of OROV infections was consistently lower than that of DENV, CHKV, and ZIKV during outbreaks (Risk Ratio [RR] 24.82, 95%CI 21.12 to 29.16; RR 2.207, 95%CI 1.427 to 3.412; and RR 7.900, 95%CI 5.386 to 11.578, respectively) and in the general population (RR 23.614, 95%CI 20.584 to 27.129; RR 3.103, 95%CI 2.056 to 4.685; and RR 49.500, 95%CI 12.256 to 199.921, respectively). In conclusion, our study stresses the possibly high underestimation of OROV prevalence in the general population of South America, the potential global threat represented by this arbovirus infection, and the potential preventive role of a comprehensive “One Health approach”. Full article

(This article belongs to the Collection Emerging Arboviruses, Volume II)

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16 pages, 4417 KiB

Open AccessArticle

A Quadruple Gene-Deleted Live BoHV-1 Subunit RVFV Vaccine Vector Reactivates from Latency and Replicates in the TG Neurons of Calves but Is Not Transported to and Shed from Nasal Mucosa

by Selvaraj Pavulraj, Rhett W. Stout, Daniel B. Paulsen and Shafiqul I. Chowdhury

Viruses 2024, 16(9), 1497; https://doi.org/10.3390/v16091497 - 21 Sep 2024

Viewed by 943

Abstract

Bovine herpesvirus type 1 (BoHV-1) establishes lifelong latency in trigeminal ganglionic (TG) neurons following intranasal and ocular infection in cattle. Periodically, the latent virus reactivates in the TG due to stress and is transported anterogradely to nerve endings in the nasal epithelium, where [...] Read more.

Bovine herpesvirus type 1 (BoHV-1) establishes lifelong latency in trigeminal ganglionic (TG) neurons following intranasal and ocular infection in cattle. Periodically, the latent virus reactivates in the TG due to stress and is transported anterogradely to nerve endings in the nasal epithelium, where the virus replicates and sheds. Consequently, BoHV-1 is transmitted to susceptible animals and maintained in the cattle population. Modified live BoHV-1 vaccine strains (BoHV-1 MLV) also have a similar latency reactivation. Therefore, they circulate and are maintained in cattle herds. Additionally, they can regain virulence and cause vaccine outbreaks because they mutate and recombine with other circulating field wild-type (wt) strains. Recently, we constructed a BoHV-1 quadruple mutant virus (BoHV-1qmv) that lacks immune evasive properties due to UL49.5 and glycoprotein G (gG) deletions. In addition, it also lacks the gE cytoplasmic tail (gE CT) and Us9 gene sequences designed to make it safe, increase its vaccine efficacy against BoHV-1, and restrict its anterograde neuronal transport noted above. Further, we engineered the BoHV-1qmv-vector to serve as a subunit vaccine against the Rift Valley fever virus (BoHV-1qmv Sub-RVFV) (doi: 10.3390/v15112183). In this study, we determined the latency reactivation and nasal virus shedding properties of BoHV-1qmv (vector) and BoHV-1qmv-vectored subunit RVFV (BoHV-1qmv sub-RVFV) vaccine virus in calves in comparison to the BoHV-1 wild-type (wt) following intranasal inoculation. The real-time PCR results showed that BoHV-1 wt- but not the BoHV-1qmv vector- and BoHV-1qmv Sub-RVFV-inoculated calves shed virus in the nose following dexamethasone-induced latency reactivation; however, like the BoHV-1 wt, both the BoHV-1qmv vector and BoHV-1qmv Sub-RVFV viruses established latency, were reactivated, and replicated in the TG neurons. These results are consistent with the anterograde neurotransport function of the gE CT and Us9 sequences, which are deleted in the BoHV-1qmv and BoHV-1qmv Sub-RVFV. Full article

(This article belongs to the Section Animal Viruses)

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7 pages, 417 KiB

Open AccessBrief Report

Evaluating the Effects of Viruses on Eastern Indigo Snakes (Drymarchon couperi) with Gastric Cryptosporidiosis

by James E. Bogan, Jr., Robert J. Ossiboff, April L. Childress, James F. X. Wellehan and Alexandra K. Mason

Viruses 2024, 16(9), 1496; https://doi.org/10.3390/v16091496 - 21 Sep 2024

Viewed by 733

Abstract

A breeding colony of wild-origin eastern indigo snakes (EISs, Drymarchon couperi) that is part of a reintroduction program has been impacted by gastric cryptosporidiosis. Gastric cryptosporidiosis is an insidious disease of squamates caused by an apicomplexan protozoan, Cryptosporidium serpentis. Viral coinfections [...] Read more.

A breeding colony of wild-origin eastern indigo snakes (EISs, Drymarchon couperi) that is part of a reintroduction program has been impacted by gastric cryptosporidiosis. Gastric cryptosporidiosis is an insidious disease of squamates caused by an apicomplexan protozoan, Cryptosporidium serpentis. Viral coinfections have been implicated as possible immunosuppressant agents that allow for disease progression and both adenovirus and reovirus have been implicated in allowing for the progression of gastric cryptosporidiosis during coinfection in other snake species. Molecular (PCR) screening for adenoviruses and reoviruses was performed for both C. serpentis-positive and C. serpentis-negative EIS within the breeding colony. No reoviruses were detected in the collection. Adenoviruses were present in 11/68 (16.2%) EISs evaluated, and there was no significant difference between C. serpentis-positive and C. serpentis-negative EISs (p = 0.196). There was no significant difference in adenovirus status between C. serpentis-positive EISs’ lifespan (p = 0.191) or survival rates (p = 0.823). These findings suggest that the presence of the adenoviruses found in this study does not contribute to the formation or progression of gastric cryptosporidiosis in EISs. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 792 KiB

Open AccessArticle

Combining Short- and Long-Read Sequencing Technologies to Identify SARS-CoV-2 Variants in Wastewater

by Gabrielle Jayme, Ju-Ling Liu, Jose Hector Galvez, Sarah Julia Reiling, Sukriye Celikkol, Arnaud N’Guessan, Sally Lee, Shu-Huang Chen, Alexandra Tsitouras, Fernando Sanchez-Quete, Thomas Maere, Eyerusalem Goitom, Mounia Hachad, Elisabeth Mercier, Stephanie Katharine Loeb, Peter A. Vanrolleghem, Sarah Dorner, Robert Delatolla, B. Jesse Shapiro, Dominic Frigon, Jiannis Ragoussis and Terrance P. Snutch Show full author list Hide full author list

Viruses 2024, 16(9), 1495; https://doi.org/10.3390/v16091495 - 21 Sep 2024

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Abstract

During the COVID-19 pandemic, the monitoring of SARS-CoV-2 RNA in wastewater was used to track the evolution and emergence of variant lineages and gauge infection levels in the community, informing appropriate public health responses without relying solely on clinical testing. As more sublineages [...] Read more.

During the COVID-19 pandemic, the monitoring of SARS-CoV-2 RNA in wastewater was used to track the evolution and emergence of variant lineages and gauge infection levels in the community, informing appropriate public health responses without relying solely on clinical testing. As more sublineages were discovered, it increased the difficulty in identifying distinct variants in a mixed population sample, particularly those without a known lineage. Here, we compare the sequencing technology from Illumina and from Oxford Nanopore Technologies, in order to determine their efficacy at detecting variants of differing abundance, using 248 wastewater samples from various Quebec and Ontario cities. Our study used two analytical approaches to identify the main variants in the samples: the presence of signature and marker mutations and the co-occurrence of signature mutations within the same amplicon. We observed that each sequencing method detected certain variants at different frequencies as each method preferentially detects mutations of distinct variants. Illumina sequencing detected more mutations with a predominant lineage that is in low abundance across the population or unknown for that time period, while Nanopore sequencing had a higher detection rate of mutations that are predominantly found in the high abundance B.1.1.7 (Alpha) lineage as well as a higher sequencing rate of co-occurring mutations in the same amplicon. We present a workflow that integrates short-read and long-read sequencing to improve the detection of SARS-CoV-2 variant lineages in mixed population samples, such as wastewater. Full article

(This article belongs to the Section Coronaviruses)

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9 pages, 937 KiB

Open AccessArticle

Validation of Saliva as the Clinical Specimen Type for a University-Wide COVID-19 Surveillance Program

by Michael L. Farrell, Anton V. Bryksin, Emily Ryan, Jessica Lin, Naima Djeddar, German Khunteev, Benjamin Holton, Miles Paca, Nicholas Speller, James T. Merrill, Ted M. Ross, Robert J. Hogan, Greg Gibson, Andrés J. García and Michael P. Shannon

Viruses 2024, 16(9), 1494; https://doi.org/10.3390/v16091494 - 21 Sep 2024

Viewed by 664

Abstract

At the beginning of the COVID-19 pandemic, the Georgia Institute of Technology made the decision to keep the university doors open for on-campus attendance. To manage COVID-19 infection rates, internal resources were applied to develop and implement a mass asymptomatic surveillance program. The [...] Read more.

At the beginning of the COVID-19 pandemic, the Georgia Institute of Technology made the decision to keep the university doors open for on-campus attendance. To manage COVID-19 infection rates, internal resources were applied to develop and implement a mass asymptomatic surveillance program. The objective was to identify infections early for proper follow-on verification testing, contact tracing, and quarantine/isolation as needed. Program success depended on frequent and voluntary sample collection from over 40,000 students, faculty, and staff personnel. At that time, the nasopharyngeal (NP) swab, not saliva, was the main accepted sample type for COVID-19 testing. However, due to collection discomfort and the inability to be self-collected, the NP swab was not feasible for voluntary and frequent self-collection. Therefore, saliva was selected as the clinical sample type and validated. A saliva collection kit and a sample processing and analysis workflow were developed. The results of a clinical sample-type comparison study between co-collected and matched NP swabs and saliva samples showed 96.7% positive agreement and 100% negative agreement. During the Fall 2020 and Spring 2021 semesters, 319,988 samples were collected and tested. The program resulted in maintaining a low overall mean positivity rate of 0.78% and 0.54% for the Fall 2020 and Spring 2021 semesters, respectively. For this high-throughput asymptomatic COVID-19 screening application, saliva was an exceptionally good sample type. Full article

(This article belongs to the Special Issue Saliva in the Diagnosis of Viral Diseases)

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20 pages, 442 KiB

Open AccessArticle

K103N, V106M and Y188L Significantly Reduce HIV-1 Subtype C Phenotypic Susceptibility to Doravirine

by Nikita Reddy, Maria Papathanasopoulos, Kim Steegen and Adriaan Erasmus Basson

Viruses 2024, 16(9), 1493; https://doi.org/10.3390/v16091493 - 20 Sep 2024

Viewed by 844

Abstract

Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with efficacy against some NNRTI-resistant mutants. Although DOR resistance mutations are established for HIV-1 subtype B, it is less clear for non-B subtypes. This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in [...] Read more.

Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with efficacy against some NNRTI-resistant mutants. Although DOR resistance mutations are established for HIV-1 subtype B, it is less clear for non-B subtypes. This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication-defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others did not significantly impact DOR susceptibility. We observed an agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y188L caused high-level resistance, in agreement with the predictions. These mutations are frequently observed in patients failing efavirenz- or nevirapine-based first-line regimens. However, they are also observed in those failing a protease inhibitor-based second-line regimen, as we have observed in our database. Genotypic drug resistance testing is therefore vital prior to the initiation of DOR-based treatment for those previously exposed to efavirenz or nevirapine. Full article

(This article belongs to the Special Issue Advances in Research on HIV Drug Resistance and Other Determinants of Treatment Success: 2nd Edition)

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16 pages, 3500 KiB

Open AccessArticle

Optimization of Cellular Transduction by the HIV-Based Pseudovirus Platform with Pan-Coronavirus Spike Proteins

by Syamala Rani Thimmiraju, Maria Jose Villar, Jason T. Kimata, Ulrich Strych, Maria Elena Bottazzi, Peter J. Hotez and Jeroen Pollet

Viruses 2024, 16(9), 1492; https://doi.org/10.3390/v16091492 - 20 Sep 2024

Viewed by 1374

Abstract

Over the past three years, new SARS-CoV-2 variants have continuously emerged, evolving to a point where an immune response against the original vaccine no longer provided optimal protection against these new strains. During this time, high-throughput neutralization assays based on pseudoviruses have become [...] Read more.

Over the past three years, new SARS-CoV-2 variants have continuously emerged, evolving to a point where an immune response against the original vaccine no longer provided optimal protection against these new strains. During this time, high-throughput neutralization assays based on pseudoviruses have become a valuable tool for assessing the efficacy of new vaccines, screening updated vaccine candidates against emerging variants, and testing the efficacy of new therapeutics such as monoclonal antibodies. Lentiviral vectors derived from HIV-1 are popular for developing pseudo and chimeric viruses due to their ease of use, stability, and long-term transgene expression. However, the HIV-based platform has lower transduction rates for pseudotyping coronavirus spike proteins than other pseudovirus platforms, necessitating more optimized methods. As the SARS-CoV-2 virus evolved, we produced over 18 variants of the spike protein for pseudotyping with an HIV-based vector, optimizing experimental parameters for their production and transduction. In this article, we present key parameters that were assessed to improve such technology, including (a) the timing and method of collection of pseudovirus supernatant; (b) the timing of host cell transduction; (c) cell culture media replenishment after pseudovirus adsorption; and (d) the centrifugation (spinoculation) parameters of the host cell+ pseudovirus mix, towards improved transduction. Additionally, we found that, for some pseudoviruses, the addition of a cationic polymer (polybrene) to the culture medium improved the transduction process. These findings were applicable across variant spike pseudoviruses that include not only SARS-CoV-2 variants, but also SARS, MERS, Alpha Coronavirus (NL-63), and bat-like coronaviruses. In summary, we present improvements in transduction efficiency, which can broaden the dynamic range of the pseudovirus titration and neutralization assays. Full article

(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)

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20 pages, 1833 KiB

Open AccessReview

Is Autophagy a Friend or Foe in SARS-CoV-2 Infection?

by Asifa Khan, Jiaxin Ling and Jinlin Li

Viruses 2024, 16(9), 1491; https://doi.org/10.3390/v16091491 - 20 Sep 2024

Viewed by 1194

Abstract

As obligate parasites, viruses need to hijack resources from infected cells to complete their lifecycle. The interaction between the virus and host determines the viral infection process, including viral propagation and the disease’s outcome. Understanding the interaction between the virus and host factors [...] Read more.

As obligate parasites, viruses need to hijack resources from infected cells to complete their lifecycle. The interaction between the virus and host determines the viral infection process, including viral propagation and the disease’s outcome. Understanding the interaction between the virus and host factors is a basis for unraveling the intricate biological processes in the infected cells and thereby developing more efficient and targeted antivirals. Among the various fundamental virus–host interactions, autophagy plays vital and also complicated roles by directly engaging in the viral lifecycle and functioning as an anti- and/or pro-viral factor. Autophagy thus becomes a promising target against virus infection. Since the COVID-19 pandemic, there has been an accumulation of studies aiming to investigate the roles of autophagy in SARS-CoV-2 infection by using different models and from distinct angles, providing valuable information for systematically and comprehensively dissecting the interplay between autophagy and SARS-CoV-2. In this review, we summarize the advancements in the studies of the interaction between SARS-CoV-2 and autophagy, as well as detailed molecular mechanisms. We also update the current knowledge on the pharmacological strategies used to suppress SARS-CoV-2 replication through remodeling autophagy. These extensive studies on SARS-CoV-2 and autophagy can advance our understanding of virus–autophagy interaction and provide insights into developing efficient antiviral therapeutics by regulating autophagy. Full article

(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)

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13 pages, 3864 KiB

Open AccessArticle

EZH2 Inhibition by DS3201 Triggers the Kaposi’s Sarcoma-Associated Herpesvirus Lytic Cycle and Potentiates the Effects Induced by SAHA in Primary Effusion Lymphoma Cells

by Roberta Gonnella, Flavia Collura, Vincenzo Corrado, Michele Di Crosta, Roberta Santarelli and Mara Cirone

Viruses 2024, 16(9), 1490; https://doi.org/10.3390/v16091490 - 20 Sep 2024

Viewed by 835

Abstract

Primary Effusion Lymphoma (PEL) cells carry Kaposi’s sarcoma-associated herpesvirus (KSHV) in a latent state, except for a small number of cells in which the virus replicates to ensure its persistence into the infected host. However, the lytic cycle can be reactivated in vitro [...] Read more.

Primary Effusion Lymphoma (PEL) cells carry Kaposi’s sarcoma-associated herpesvirus (KSHV) in a latent state, except for a small number of cells in which the virus replicates to ensure its persistence into the infected host. However, the lytic cycle can be reactivated in vitro by exposing these lymphoma cells to various treatments, leading to cell lysis. To restrict viral antigen expression, KSHV induces repressive epigenetic changes, including DNA methylation and histone modifications. Among the latter, histone deacetylation and tri-methylation of Histone H3 lisyne-27 (H3K27me3) have been reported to play a role. Here, we found that the inhibition of H3K27 tri-methylation by valemetostat DS3201 (DS), a small molecule that inhibits Enhancer of Zeste Homolog 2 (EZH2) methyltransferase, induced the KSHV lytic cycle in PEL cells, and that this effect involved the activation of the wtp53–p21 axis and autophagic dysregulation. DS also potentiated the lytic cycle activation mediated by the Histone deacetylases (HDAC) inhibitor Suberoylanilide hydroxamic acid (SAHA) and reinforced its cytotoxic effect, suggesting that such a combination could be used to unbalance the latent/lytic cycle and further impair the survival of PEL cells. Full article

(This article belongs to the Special Issue Molecular and Cellular Biology of Human Oncogenic Viruses)

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12 pages, 595 KiB

Open AccessReview

RNAi-Induced Gene Silencing against Chikungunya and COVID-19: What Have We Learned So Far, and What Is the Way Forward?

by Kingshuk Panda, Kalichamy Alagarasu, Rajarshee Tagore, Mandar Paingankar, Satyendra Kumar, Manish Kumar Jeengar, Sarah Cherian and Deepti Parashar

Viruses 2024, 16(9), 1489; https://doi.org/10.3390/v16091489 - 20 Sep 2024

Viewed by 1123

Abstract

RNA interference (RNAi) is a process in which small RNA molecules (such as small interfering RNAs or siRNAs) bind to specific messenger RNAs (mRNAs), leading to its degradation and inhibition of protein synthesis. Our studies have shown that RNAi can effectively silence genes [...] Read more.

RNA interference (RNAi) is a process in which small RNA molecules (such as small interfering RNAs or siRNAs) bind to specific messenger RNAs (mRNAs), leading to its degradation and inhibition of protein synthesis. Our studies have shown that RNAi can effectively silence genes involved in the replication of the Chikungunya virus (CHIKV) in cells. However, these investigations were performed only in laboratory settings and have yet to be tested in human clinical trials. Researchers need to conduct more research to determine the safety and efficacy of RNAi-based therapies as a therapeutic agent to treat viral infections. In this review, the history of evolution of siRNA as an inhibitor of protein synthesis, along with its current developments, is discussed based on our experience. Moreover, this review examines the hurdles and future implications associated with siRNA based therapeutic approaches. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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13 pages, 3790 KiB

Open AccessArticle

Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi

by Benjamin Morgan, Eleanor A. Lyons, Amanda Handley, Nada Bogdanovic-Sakran, Daniel Pavlic, Desiree Witte, Jonathan Mandolo, Ann Turner, Khuzwayo C. Jere, Frances Justice, Darren Suryawijaya Ong, Rhian Bonnici, Karen Boniface, Celeste M. Donato, Ashley Mpakiza, Anell Meyer, Naor Bar-Zeev, Miren Iturriza-Gomara, Nigel A. Cunliffe, Margaret Danchin and Julie E. Bines Show full author list Hide full author list

Viruses 2024, 16(9), 1488; https://doi.org/10.3390/v16091488 - 19 Sep 2024

Cited by 1 | Viewed by 1172

Abstract

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This [...] Read more.

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease. Full article

(This article belongs to the Special Issue Rotaviruses and Rotavirus Vaccines)

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19 pages, 4045 KiB

Open AccessArticle

Differing Transcriptomic Responses in High Titer versus Low Titer Aedes aegypti Mosquitoes after Oral Infection with Sindbis Virus

by Peter Hodoameda, Robert E. Ditter, Scott R. Santos and Rollie J. Clem

Viruses 2024, 16(9), 1487; https://doi.org/10.3390/v16091487 - 19 Sep 2024

Viewed by 825

Abstract

Oral infection of mosquitoes by arboviruses often results in a large degree of variation in the amount of infectious virus between individual mosquitoes, even when the mosquitoes are from inbred laboratory strains. This variability in arbovirus load has been shown to affect virus [...] Read more.

Oral infection of mosquitoes by arboviruses often results in a large degree of variation in the amount of infectious virus between individual mosquitoes, even when the mosquitoes are from inbred laboratory strains. This variability in arbovirus load has been shown to affect virus transmissibility. Previously, our group described population genetic and specific infectivity differences between the virus populations found in high and low titer Aedes aegypti mosquitoes that had been orally infected with Sindbis virus (SINV). In this study, we sought to investigate whether there were also differences in transcriptomic response between these high and low titer mosquitoes. Results from the transcriptomic data analysis showed that more genes involved in antiviral activity, endopeptidase activity, and methyltransferase activity were upregulated in low titer mosquitoes than in high titer mosquitoes, relative to blood-fed controls. Meanwhile, genes involved in ion transport, energy metabolism, acetylation, glycosylation, lipid metabolism, and transport tended to be upregulated in high titer mosquitoes more than in low titer mosquitoes, relative to blood-fed mosquitoes. Overall, genes involved in antiviral activities tended to be upregulated in low titer mosquitoes while genes involved in proviral activities were mostly upregulated in high titer mosquitoes. This study has identified a number of candidate mosquito genes that are putatively associated with SINV titer variability after oral infection of Ae. aegypti, and these can now be investigated in order to ascertain their roles in virus replication and their contributions to determining vector competence. Full article

(This article belongs to the Section Invertebrate Viruses)

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25 pages, 8538 KiB

Open AccessArticle

Extensive Diversity of Viruses in Millipedes Collected in the Dong Nai Biosphere Reserve (Vietnam)

by Alexander G. Litov, Irina I. Semenyuk, Oxana A. Belova, Alexandra E. Polienko, Nguyen Van Thinh, Galina G. Karganova and Alexei V. Tiunov

Viruses 2024, 16(9), 1486; https://doi.org/10.3390/v16091486 - 19 Sep 2024

Viewed by 1176

Abstract

Advances in sequencing technologies and bioinformatics have led to breakthroughs in the study of virus biodiversity. Millipedes (Diplopoda, Myriapoda, Arthropoda) include more than 12,000 extant species, yet data on virus diversity in Diplopoda are scarce. This study aimed to explore the virome of [...] Read more.

Advances in sequencing technologies and bioinformatics have led to breakthroughs in the study of virus biodiversity. Millipedes (Diplopoda, Myriapoda, Arthropoda) include more than 12,000 extant species, yet data on virus diversity in Diplopoda are scarce. This study aimed to explore the virome of the millipedes collected in the Dong Nai Biosphere Reserve in Vietnam. We studied 14 species of millipedes and managed to assemble and annotate the complete coding genomes of 16 novel viruses, the partial coding genomes of 10 more viruses, and several fragmented viral sequences, which may indicate the presence of about 54 more viruses in the studied samples. Among the complete and partial genomes, 27% were putative members of the order Picornavirales. Most of the discovered viruses were very distant from the viruses currently present in the relevant databases. At least eight viruses meet the criteria to be recognized as a new species by the International Committee on Taxonomy of Viruses, and, for two of them, a higher taxonomic status (genus and even family) can be suggested. Full article

(This article belongs to the Section Invertebrate Viruses)

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13 pages, 1565 KiB

Open AccessArticle

Hepatocellular Carcinoma Incidences and Risk Factors in Hepatitis C Patients: Interferon versus Direct-Acting Agents

by Yu-Ting Kao, Yen-Chun Liu, Ya-Ting Cheng, Yu-Wen Wen, Yi-Chung Hsieh, Cheng-Er Hsu, Chung-Wei Su, Jennifer Chia-Hung Tai, Yi-Cheng Chen, Wen-Juei Jeng, Chun-Yen Lin, Rong-Nan Chien, Dar-In Tai and I-Shyan Sheen

Viruses 2024, 16(9), 1485; https://doi.org/10.3390/v16091485 - 18 Sep 2024

Viewed by 890

Abstract

Background: Hepatocellular carcinoma (HCC) remains a significant concern for patients with chronic hepatitis C (HCV), even after achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs) or interferon (IFN)-based therapies. This study compared the risk of HCC in patients with HCV who [...] Read more.

Background: Hepatocellular carcinoma (HCC) remains a significant concern for patients with chronic hepatitis C (HCV), even after achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs) or interferon (IFN)-based therapies. This study compared the risk of HCC in patients with HCV who achieved SVR through the DAA versus IFN regimens. Methods: A retrospective analysis was conducted on 4806 HCV patients, without coinfection nor prior HCC history, treated at the Chang Gung Memorial Hospital, Taiwan (DAA: 2825, IFN: 1981). Kaplan–Meier and Cox regression analyses with propensity score matching (PSM) were used to adjust for baseline differences. Results: DAA-treated patients exhibited a higher incidence of HCC than IFN-treated patients before and after PSM (after PSM: annual: 1% vs. 0.5%; 6-year: 6% vs. 3%, p = 0.01). Both DAA and IFN patients had a decreased HCC incidence during follow-up (>3 vs. <3 years from the end of treatment: DAA: 1.43% vs. 1.00% per year; IFN: 0.47% vs. 0.36% per year, both p < 0.05). HCC incidence was higher in the first three years post-SVR in DAA-treated ACLD patients and then decreased (3.26% vs. 1.39% per year, p < 0.01). In contrast, HCC incidence remained constant in the non-ACLD and IFN-treated groups. Multivariate Cox regression identified age ≥ 60, male sex, BMI, AFP ≥ 6 ng/mL, FIB-4, and ACLD status as independent risk factors for HCC, but antiviral regimens were not an independent factor for HCC. Conclusion: DAA treatment significantly affects HCC risk primarily within three years post-treatment, especially in younger HCV patients with ACLD. HCC incidence was reduced after three years in ACLD patients treated by DAA, but continued surveillance was still necessary. However, patients under 60 without advanced liver disease may require less intensive follow-up. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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43 pages, 4738 KiB

Open AccessReview

New Therapies and Strategies to Curb HIV Infections with a Focus on Macrophages and Reservoirs

by Maria Marra, Alessia Catalano, Maria Stefania Sinicropi, Jessica Ceramella, Domenico Iacopetta, Romina Salpini, Valentina Svicher, Stefania Marsico, Stefano Aquaro and Michele Pellegrino

Viruses 2024, 16(9), 1484; https://doi.org/10.3390/v16091484 - 18 Sep 2024

Cited by 1 | Viewed by 2097

Abstract

More than 80 million people worldwide have been infected with the human immunodeficiency virus (HIV). There are now approximately 39 million individuals living with HIV/acquired immunodeficiency syndrome (AIDS). Although treatments against HIV infection are available, AIDS remains a serious disease. Combination antiretroviral therapy [...] Read more.

More than 80 million people worldwide have been infected with the human immunodeficiency virus (HIV). There are now approximately 39 million individuals living with HIV/acquired immunodeficiency syndrome (AIDS). Although treatments against HIV infection are available, AIDS remains a serious disease. Combination antiretroviral therapy (cART), also known as highly active antiretroviral therapy (HAART), consists of treatment with a combination of several antiretroviral drugs that block multiple stages in the virus replication cycle. However, the increasing usage of cART is inevitably associated with the emergence of HIV drug resistance. In addition, the development of persistent cellular reservoirs of latent HIV is a critical obstacle to viral eradication since viral rebound takes place once anti-retroviral therapy (ART) is interrupted. Thus, several efforts are being applied to new generations of drugs, vaccines and new types of cART. In this review, we summarize the antiviral therapies used for the treatment of HIV/AIDS, both as individual agents and as combination therapies, and highlight the role of both macrophages and HIV cellular reservoirs and the most recent clinical studies related to this disease. Full article

(This article belongs to the Special Issue Roles of Macrophages in Viral Infections)

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22 pages, 422 KiB

Open AccessReview

Mycologists and Virologists Align: Proposing Botrytis cinerea for Global Mycovirus Studies

by Mahmoud E. Khalifa, María A. Ayllón, Lorena Rodriguez Coy, Kim M. Plummer, Anthony R. Gendall, Kar Mun Chooi, Jan A.L. van Kan and Robin M. MacDiarmid

Viruses 2024, 16(9), 1483; https://doi.org/10.3390/v16091483 - 18 Sep 2024

Viewed by 1663

Abstract

Mycoviruses are highly genetically diverse and can significantly change their fungal host’s phenotype, yet they are generally under-described in genotypic and biological studies. We propose Botrytis cinerea as a model mycovirus system in which to develop a deeper understanding of mycovirus epidemiology including [...] Read more.

Mycoviruses are highly genetically diverse and can significantly change their fungal host’s phenotype, yet they are generally under-described in genotypic and biological studies. We propose Botrytis cinerea as a model mycovirus system in which to develop a deeper understanding of mycovirus epidemiology including diversity, impact, and the associated cellular biology of the host and virus interaction. Over 100 mycoviruses have been described in this fungal host. B. cinerea is an ideal model fungus for mycovirology as it has highly tractable characteristics—it is easy to culture, has a worldwide distribution, infects a wide range of host plants, can be transformed and gene-edited, and has an existing depth of biological resources including annotated genomes, transcriptomes, and isolates with gene knockouts. Focusing on a model system for mycoviruses will enable the research community to address deep research questions that cannot be answered in a non-systematic manner. Since B. cinerea is a major plant pathogen, new insights may have immediate utility as well as creating new knowledge that complements and extends the knowledge of mycovirus interactions in other fungi, alone or with their respective plant hosts. In this review, we set out some of the critical steps required to develop B. cinerea as a model mycovirus system and how this may be used in the future. Full article

(This article belongs to the Special Issue Diversity and Coinfections of Plant or Fungal Viruses, 3rd Edition)

20 pages, 4776 KiB

Open AccessArticle

The Autonomous Fusion Activity of Human Cytomegalovirus Glycoprotein B Is Regulated by Its Carboxy-Terminal Domain

by Nina Reuter, Barbara Kropff, Xiaohan Chen, William J. Britt, Heinrich Sticht, Michael Mach and Marco Thomas

Viruses 2024, 16(9), 1482; https://doi.org/10.3390/v16091482 - 18 Sep 2024

Viewed by 819

Abstract

The human cytomegalovirus (HCMV) glycoprotein B (gB) is the viral fusogen required for entry into cells and for direct cell-to-cell spread of the virus. We have previously demonstrated that the exchange of the carboxy-terminal domain (CTD) of gB for the CTD of the [...] Read more.

The human cytomegalovirus (HCMV) glycoprotein B (gB) is the viral fusogen required for entry into cells and for direct cell-to-cell spread of the virus. We have previously demonstrated that the exchange of the carboxy-terminal domain (CTD) of gB for the CTD of the structurally related fusion protein G of the vesicular stomatitis virus (VSV-G) resulted in an intrinsically fusion-active gB variant (gB/VSV-G). In this present study, we employed a dual split protein (DSP)-based cell fusion assay to further characterize the determinants of fusion activity in the CTD of gB. We generated a comprehensive library of gB CTD truncation mutants and identified two mutants, gB-787 and gB-807, which were fusion-competent and induced the formation of multinucleated cell syncytia in the absence of other HCMV proteins. Structural modeling coupled with site-directed mutagenesis revealed that gB fusion activity is primarily mediated by the CTD helix 2, and secondarily by the recruitment of cellular SH2/WW-domain-containing proteins. The fusion activity of gB-807 was inhibited by gB-specific monoclonal antibodies (MAbs) targeting the antigenic domains AD-1 to AD-5 within the ectodomain and not restricted to MAbs directed against AD-4 and AD-5 as observed for gB/VSV-G. This finding suggested a differential regulation of the fusion-active conformational state of both gB variants. Collectively, our findings underscore a pivotal role of the CTD in regulating the fusogenicity of HCMV gB, with important implications for understanding the conformations of gB that facilitate membrane fusion, including antigenic structures that could be targeted by antibodies to block this essential step in HCMV infection. Full article

(This article belongs to the Special Issue Research on Herpes Virus Fusion and Entry)

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17 pages, 2477 KiB

Open AccessArticle

Immunogenicity of an Inactivated COVID-19 Vaccine in People Living with HIV in Guangxi, China: A Prospective Cohort Study

by Yuting Wu, Xinwei Wang, Yunxuan Huang, Rongfeng Chen, Yuexiang Xu, Wudi Wei, Fengxiang Qin, Zongxiang Yuan, Jinming Su, Xiu Chen, Jie Liu, Liufang Wen, Minjuan Shi, Tongxue Qin, Yinlu Liao, Beibei Lu, Xing Tao, Cuixiao Wang, Shanshan Chen, Jinmiao Li, William J. Liu, Li Ye, Hao Liang and Junjun Jiang Show full author list Hide full author list

Viruses 2024, 16(9), 1481; https://doi.org/10.3390/v16091481 - 18 Sep 2024

Viewed by 951

Abstract

The inactivated COVID-19 vaccine has demonstrated high efficacy in the general population through extensive clinical and real-world studies. However, its effectiveness in immunocompromised individuals, particularly those living with HIV (PLWH), remains limited. In this study, 20 PLWH and 15 HIV-seronegative individuals were recruited [...] Read more.

The inactivated COVID-19 vaccine has demonstrated high efficacy in the general population through extensive clinical and real-world studies. However, its effectiveness in immunocompromised individuals, particularly those living with HIV (PLWH), remains limited. In this study, 20 PLWH and 15 HIV-seronegative individuals were recruited to evaluate the immunogenicity of an inactivated COVID-19 vaccine in PLWH through a prospective cohort study. The median age of the 20 PLWH and 15 HIV-seronegative individuals was 42 years and 31 years, respectively. Of the PLWH, nine had been on ART for over five years. The median anti-SARS-CoV-2 S-RBD IgG antibody level on d₂₂₄ was higher than that on d₄₂ (8188.7 ng/mL vs. 3200.9 ng/mL, P < 0.05). Following COVID-19 infection, the antibody level increased to 29,872.5 ng/mL on d_re+90, 12.19 times higher than that on d₃₀₀. Compared with HIV-seronegative individuals, the antibody level in PLWH was lower on d₂₁₀ (183.3 ng/mL vs. 509.3 ng/mL, P < 0.01), while there was no difference after d₂₂₄. The symptoms of COVID-19 infection in PLWH were comparable to those in HIV-seronegative individuals. In this study, the inactivated COVID-19 vaccine demonstrated good immunogenicity in PLWH. The protective benefit of booster vaccinations for PLWH cannot be ignored. Implementing a booster vaccination policy for PLWH is an effective approach to providing better protection against the COVID-19 pandemic. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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14 pages, 3745 KiB

Open AccessArticle

Sputnik V-Induced Antibodies against SARS-CoV-2 Variants during the Dissemination of the Gamma Variant in Venezuela

by Christopher Franco, Alejandro Cornejo, Mariajosé Rodríguez, Alexis García, Inirida Belisario, Soriuska Mayora, Domingo José Garzaro, Rossana Celeste Jaspe, Mariana Hidalgo, Nereida Parra, Ferdinando Liprandi, José Luis Zambrano, Héctor Rafael Rangel and Flor Helene Pujol

Viruses 2024, 16(9), 1480; https://doi.org/10.3390/v16091480 - 18 Sep 2024

Cited by 1 | Viewed by 812

Abstract

The COVID-19 pandemic was characterized by the emergence and succession of SARS-CoV-2 variants able to evade the antibody response induced by natural infection and vaccination. To evaluate the IgG reactivity and neutralizing capacity of the serum of individuals vaccinated with Sputnik V (105 [...] Read more.

The COVID-19 pandemic was characterized by the emergence and succession of SARS-CoV-2 variants able to evade the antibody response induced by natural infection and vaccination. To evaluate the IgG reactivity and neutralizing capacity of the serum of individuals vaccinated with Sputnik V (105 volunteers vaccinated) against different viral variants. IgG reactivity to the Spike protein (S) was evaluated by ELISA. A plaque reduction neutralization test was performed using different viral variant isolates. At 42 days post-vaccination, the frequency of recognition and reactivity to the S protein of the Omicron variant was lower compared to that of the other variants. In general, a higher average neutralization titer was seen against the ancestral variant compared to the variants, especially Omicron. However, some sera exhibited a higher neutralization titer to the Gamma variant compared to the ancestral variant, suggesting unapparent exposure during the clinical trial. Antibodies induced by Sputnik V can recognize, persist, and neutralize SARS-CoV-2 variants, with Omicron being the one that best evades this response. These results represent a unique report on the humoral response induced by a globally lesser-studied vaccine in terms of efficacy and immune escape, offering insights into developing vaccines targeting unknown coronaviruses. Full article

(This article belongs to the Special Issue Host Cell-Virus Interaction, 3rd Edition)

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8 pages, 1615 KiB

Open AccessBrief Report

The Discovery of a Citrus Yellow Vein Clearing Virus Hacienda Heights Isolate Diversifies the Geological Origins of the Virus in California, United States

by Yong-Duo Sun and Raymond Yokomi

Viruses 2024, 16(9), 1479; https://doi.org/10.3390/v16091479 - 18 Sep 2024

Viewed by 729

Abstract

The citrus yellow vein clearing virus (CYVCV) is an emerging threat to the U.S. citrus industry. Reports from China shows it cause significant reductions in fruit yield and growth, particularly in lemon trees. In 2022, CYVCV was detected in a wide range of [...] Read more.

The citrus yellow vein clearing virus (CYVCV) is an emerging threat to the U.S. citrus industry. Reports from China shows it cause significant reductions in fruit yield and growth, particularly in lemon trees. In 2022, CYVCV was detected in a wide range of citrus cultivars in localized urban properties in Tulare, California. In 2024, a CYVCV-infected lemon tree was detected in Hacienda Heights in Los Angeles County, California, geographically separated from the Tulare foci. Through long-read sequencing technology, the whole-genome sequence of a CYVCV isolate from Hacienda Heights (designated as CYVCV-CA-HH1, Accession number PP840891.1) was obtained. Sequence alignments and neighbornet analysis strongly suggested that the CYVCV-CA-HH1 isolate has a different origin than the Tulare CYVCV (CYVCV CA-TL) isolates. The CYVCV CA-TL isolates were grouped with those from South Asia (India and Pakistan) and the Middle East (Türkiye), while the CYVCV-CA-HH1 isolate was grouped with isolates from East Asia (China and South Korea). Maximum likelihood phylogenetic analysis further supports this finding, showing that the CYVCV-CA-HH1 isolate shares the most recent common ancestor with a South Korean lineage, which derives from Chinese isolates. Together, our data suggest a diverse geological origin of CYVCV isolates in California. Full article

(This article belongs to the Special Issue Emerging Fruit and Vegetable Viruses 2023)

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11 pages, 2591 KiB

Open AccessBrief Report

Insights into the Role of VPS39 and Its Interaction with CP204L and A137R in ASFV Infection

by Katarzyna Magdalena Dolata and Axel Karger

Viruses 2024, 16(9), 1478; https://doi.org/10.3390/v16091478 - 17 Sep 2024

Viewed by 873

Abstract

The African swine fever virus (ASFV) is a large and complex DNA virus that causes a highly lethal disease in swine, for which no antiviral drugs or vaccines are currently available. Studying viral–host protein–protein interactions advances our understanding of the molecular mechanisms underlying [...] Read more.

The African swine fever virus (ASFV) is a large and complex DNA virus that causes a highly lethal disease in swine, for which no antiviral drugs or vaccines are currently available. Studying viral–host protein–protein interactions advances our understanding of the molecular mechanisms underlying viral replication and pathogenesis and can facilitate the discovery of antiviral therapeutics. In this study, we employed affinity tagging and purification mass spectrometry to characterize the interactome of VPS39, an important cellular factor during the early phase of ASFV replication. The interaction network of VPS39 revealed associations with mitochondrial proteins involved in membrane contact sites formation and cellular respiration. We show that the ASFV proteins CP204L and A137R target VPS39 by interacting with its clathrin heavy-chain functional domain. Furthermore, we elaborate on the potential mechanisms by which VPS39 may contribute to ASFV replication and prioritize interactions for further investigation into mitochondrial protein function in the context of ASFV infection. Full article

(This article belongs to the Special Issue African Swine Fever Virus 4.0)

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21 pages, 3252 KiB

Open AccessArticle

Identification and Characterization of Novel Serpentoviruses in Viperid and Elapid Snakes

by Steven B. Tillis, Sarah B. Chaney, Esther E. V. Crouch, Donal Boyer, Kevin Torregrosa, Avishai D. Shuter, Anibal Armendaris, April L. Childress, Denise McAloose, Jean A. Paré, Robert J. Ossiboff and Kenneth J. Conley

Viruses 2024, 16(9), 1477; https://doi.org/10.3390/v16091477 - 17 Sep 2024

Viewed by 965

Abstract

Viruses in the subfamily Serpentovirinae (order Nidovirales, family Tobaniviridae) can cause significant morbidity and mortality in captive snakes, but documented infections have been limited to snakes of the Boidae, Colubridae, Homalopsidae, and Pythonidae families. Infections can either be [...] Read more.

Viruses in the subfamily Serpentovirinae (order Nidovirales, family Tobaniviridae) can cause significant morbidity and mortality in captive snakes, but documented infections have been limited to snakes of the Boidae, Colubridae, Homalopsidae, and Pythonidae families. Infections can either be subclinical or associated with oral and/or respiratory disease. Beginning in June 2019, a population of over 150 confiscated snakes was screened for serpentovirus as part of a quarantine disease investigation. Antemortem oropharyngeal swabs or lung tissue collected postmortem were screened for serpentovirus by PCR, and 92/165 (56.0%) of snakes tested were positive for serpentovirus. Serpentoviruses were detected in fourteen species of Viperidae native to Asia, Africa, and South America and a single species of Elapidae native to Australia. When present, clinical signs included thin body condition, abnormal behavior or breathing, stomatitis, and/or mortality. Postmortem findings included variably severe inflammation, necrosis, and/or epithelial proliferation throughout the respiratory and upper gastrointestinal tracts. Genetic characterization of the detected serpentoviruses identified four unique viral clades phylogenetically distinct from recognized serpentovirus genera. Pairwise uncorrected distance analysis supported the phylogenetic analysis and indicated that the viper serpentoviruses likely represent the first members of a novel genus in the subfamily Serpentovirinae. The reported findings represent the first documentation of serpentoviruses in venomous snakes (Viperidae and Elapidae), greatly expanding the susceptible host range for these viruses and highlighting the importance of serpentovirus screening in all captive snake populations. Full article

(This article belongs to the Special Issue Virus Discovery, Classification and Characterization)

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Viruses, Volume 16, Issue 9 (September 2024) – 160 articles

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