Search Results (108)

Loop-mediated isothermal amplification (LAMP) is a highly effective molecular diagnostic technique, particularly advantageous for point-of-care (POC) settings. In recent years, LAMP has expanded to include various adaptations such as DARQ-LAMP, QUASR, FLOS-LAMP, displacement probes and molecular beacons. These methods enable multiplex detection of multiple targets in a single reaction, enhancing cost-effectiveness and diagnostic efficiency. Consequently, LAMP has gained significant traction in diagnosing diverse viruses, notably during the COVID-19 pandemic. However, its application for detecting Herpesviridae remains relatively unexplored. This group of viruses is of particular interest due to their latency and potential reactivation, crucial for immunocompromised patients, including organ and hematopoietic stem cell transplant recipients. This review highlights recent advancements in LAMP for virus diagnosis and explores current research trends and future prospects, emphasizing the detection challenges posed by Herpesviridae. Full article

Background The facial nerve (FN) plays a pivotal role in human life; apart from its sensory and parasympathetic functions, it innervates the facial muscles, and it is therefore involved in non-verbal communication, allowing us to express emotions and reactions. Especially in the case of childhood onset, FN dysfunction can severely affect the quality of life. Methods The aim of this review is to analyze the most recent literature, focusing on the acute onset of peripheral FN palsy among pediatric patients, discussing the different etiologies, prognoses, and management strategies. A total of 882 papers were initially identified, but only 7 met the selection criteria. Therefore, data on 974 children in total were pooled and analyzed. Results According to the findings of this review, FN palsy is idiopathic in most cases, while an infective etiology was identified as the second most common. The main pathogen agents identified were Borrelia Burgdorferi, especially in endemic areas, and Herpesviridae. Respiratory tract infections and/or ear infections were also described. Head trauma or direct injury of the FN accounted for 2% of all cases. Conclusions The overall FN recovery rate is high, even though the etiology remains unknown for most patients. Therapeutic indications are still lacking, especially in the case of non-recovering FN palsy. In our opinion, large, prospective studies are necessary for improving our knowledge of this disorder and establishing evidence-based approaches. Full article

Apical lesions are diseases of infectious origin that can cause destruction of the surrounding periapical tissue, including bone tissue and periodontal ligaments, resulting in the loss of the affected teeth. Currently, the microorganisms present in pulp and apical disease are mostly studied as bacteria. However, in recent years, interest has been aroused in the study of viruses that could be present in apical lesions, and how these could affect the progression of disease. In the present study, we conducted a systematic review of the literature to evaluate and synthesize the scientific evidence on the presence of viruses and their possible role in pulpal and apical disease. This systematic review was performed according to the PRISMA reporting guidelines. The search for studies was performed in the PubMed and Web of Science databases. A total of seven studies published in the last 10 years were included. The types of samples used for virus analysis varied from one study to another. In all the included studies, the presence of any of the types of viruses studied was found, either in pulp or apical tissue. Herpesviridae family, Epstein–Barr virus (EBV) and Human cytomegalovirus (HCMV) stood out as the most commonly present in apical lesions. Further studies are required to clarify and understand the pathogenic role of viruses in pulpal and periapical disease. Full article

The Herpesviridae include the Epstein–Barr Virus (EBV) and the Kaposi Sarcoma-associated Herpesvirus (KSHV), both of which are oncogenic gamma-herpesviruses. These viruses manipulate host cellular mechanisms, including through ubiquitin-mediated pathways, to promote viral replication and oncogenesis. Ubiquitin, a regulatory protein which tags substrates for degradation or alters their function, is manipulated by both EBV and KSHV to facilitate viral persistence and cancer development. EBV infects approximately 90% of the global population and is implicated in malignancies including Burkitt lymphoma (BL), Hodgkin lymphoma (HL), post-transplant lymphoproliferative disorder (PTLD), and nasopharyngeal carcinoma. EBV latency proteins, notably LMP1 and EBNA3C, use ubiquitin-mediated mechanisms to inhibit apoptosis, promote cell proliferation, and interfere with DNA repair, contributing to tumorigenesis. EBV’s lytic proteins, including BZLF1 and BPLF1, further disrupt cellular processes to favor oncogenesis. Similarly, KSHV, a causative agent of Kaposi’s Sarcoma and lymphoproliferative disorders, has a latency-associated nuclear antigen (LANA) and other latency proteins that manipulate ubiquitin pathways to degrade tumor suppressors, stabilize oncogenic proteins, and evade immune responses. KSHV’s lytic cycle proteins, such as RTA and Orf64, also use ubiquitin-mediated strategies to impair immune functions and promote oncogenesis. This review explores the ubiquitin-mediated interactions of EBV and KSHV proteins, elucidating their roles in viral oncogenesis. Understanding these mechanisms offers insights into the similarities between the viruses, as well as provoking thought about potential therapeutic targets for herpesvirus-associated cancers. Full article

Human Herpesviruses (HHVs) play a significant role in neurological diseases such as encephalitis and meningitis, adding significant morbidity. This study aims to retrospectively analyze the effect of HHVs on patients with neurological symptoms, focusing on the Herpesviridae family’s contributions to central nervous system (CNS) infections. Methods: This retrospective cohort study included 895 patients suspected of viral CNS infections, utilizing molecular diagnosis via qPCR to identify HHVs in cerebrospinal fluid (CSF) samples. This was conducted at a reference tertiary care hospital for infectious diseases in the western Brazilian Amazon from January 2015 to December 2022, focusing on the Herpesviridae family’s clinical repercussions and of Cytomegalovirus in CNS infections. Results: The findings revealed that 7.5% of the analyzed samples tested positive for HHVs, with Human Cytomegalovirus (HCMV) and Epstein–Barr Virus (EBV) being the most prevalent. A significant association was found between HHVs and neurological diseases such as encephalitis and meningitis, especially among people living with HIV/AIDS (PLWHA), highlighting the opportunistic nature of these viruses. The study underscores the critical role of CSF analysis in diagnosing CNS infections and the complexity of managing these infections in HIV patients due to their immunocompromised status. Conclusions: The results emphasize the need for comprehensive diagnostic approaches and tailored treatment strategies for CNS infections in immunocompromised individuals. The study calls for ongoing research and advancements in clinical practice to improve patient outcomes facing CNS infections, particularly those caused by HHVs. Full article

The Macavirus genus, Gammaherpesvirinae subfamily, Herpesviridae family, contains ovine gammaherpesvirus 2 (OvGHV2), the cause of sheep-associated malignant catarrhal fever (SA-MCF). Members of the Macavirus genus associated with the development of malignant catarrhal fever (MCF) in their respective hosts share the 15A antigenic epitope, are conserved within the DNA polymerase gene and are collectively referred to as the malignant catarrhal fever virus (MCFV) complex. The ability of MCFV and/or OvGHV2 to produce abortions in ruminants is currently unknown, with little documentation of infections by these agents in bovine fetuses. This report presents the findings observed due to the detection of OvGHV2 DNA and MCFV tissue antigens in aborted bovine fetuses from southern Brazil. Four aborted bovine fetuses from three farms, located in a geographical region of Paraná State with elevated immunohistochemical (IHC) prevalence of MCFV tissue antigens, with gestational ages varying between 78 to 208 days were investigated. Significant gross and histopathological alterations were not observed in any of these fetuses. An IHC assay using the 15A-monoclonal antibody (15A-MAb), which is based on the 15A antigenic epitope of Macavirus, identified MCFV tissue antigens in multiple organs from two fetuses (#1 and #4); however, positive immunoreactivity to the 15A-MAb IHC assay was not detected in Fetus #2 and #3. Molecular testing amplified OvGHV2 DNA only from the myocardium and lungs of Fetus #1 that had positive intracytoplasmic immunoreactivity to the 15A-MAb IHC assay in these tissues. Furthermore, infections by Leptospira spp. were confirmed by molecular assays in fetuses #1, #3, and #4, while PCR detected Neospora caninum in the myocardium of Fetus #2. Additionally, molecular assays to identify well-known fetopathy agents of cattle, including bovine viral diarrhea virus, bovine alphaherpesvirus 1, Histophilus somni, and Listeria monocytogenes, did not amplify the nucleic acids of these pathogens. PCR assays to identify bovine gammaherpesvirus 6 (BoGHV6), another Macavirus known to infect cattle in Brazil, were unsuccessful. These findings confirmed that the 15A-MAb IHC assay can be efficiently used to detect MCFV antigens in organs of aborted bovine fetuses. The identification of MCFV antigens with the simultaneous detection of OvGHV2 DNA confirmed that Fetus #1 was infected by OvGHV2 and added to the few descriptions of this infection in aborted fetuses of ruminants worldwide. Moreover, the IHC detection of MCFV in multiple organs of Fetus #4, without the molecular detection of OvGHV2 or BoGHV6, may suggest that this fetus was infected by a Macavirus that was not previously diagnosed in cattle herds from Brazil. These findings strongly suggest that OvGHV2 and MCFV can produce transplacental infections in cattle. Full article

We describe a case of an immunocompetent adult male patient originally from the Democratic Republic of Congo (DRC), who was referred to our unit for a several-day history of fever and a pruritic, vesicular rash. There was initial concern in the Emergency Department for Mpox (formerly known as “monkeypox”) given the current epidemiology versus other viral etiologies. Primary varicella zoster virus (pVZV) infection was ultimately diagnosed by PCR from a swabbed, unroofed lesion, and he recovered completely with supportive management and without antiviral therapy. We herein describe how common viral exanthems may best be differentiated in an emergency or outpatient setting. Full article

Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. Methods: A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. Results: A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133–595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. Conclusion: viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children. Full article

Background: Pulmonary superinfections with Herpesviridae and Aspergillus spp. are common in severe coronavirus disease 2019 (COVID-19) pneumonia but their epidemiology and impact remain poorly understood. Methods: We conducted a retrospective observational study of 61 mechanically ventilated COVID-19 patients at Deventer Hospital’s ICU (2020–2021) who underwent bronchoalveolar lavage (BL) due to clinical deterioration. We analyzed blood and respiratory samples, treatment, and clinical outcomes. Results: Among 61 mechanically ventilated COVID-19 patients who underwent BL, 34 (55.7%) had superinfections, with 18 having COVID-19-associated pulmonary aspergillosis (CAPA), 7 having herpes simplex virus (HSV) infection, and 9 having both. Patients with HSV had later diagnoses (median 14 vs. 8 days, p = 0.014), longer mechanical ventilation (median 47 vs. 18.5 days, p = 0.015), and longer ICU stays (median 74 vs. 24 days, p = 0.021) compared to CAPA patients. At baseline, laboratory parameters and treatment (dexamethasone or tocilizumab) showed no significant association with superinfections. Mortality did not differ significantly among groups. Conclusion: In mechanically ventilated COVID-19 patients undergoing bronchoalveolar lavage, HSV reactivation occurred later in the course of illness and was associated with longer mechanical ventilation and ICU stays compared to CAPA. Baseline parameters did not predict superinfections. Full article

Some researchers have speculated that the prostatic microbiome is involved in the development of prostate cancer (PCa) but there is no consensus on certain microbiota in the prostatic tissue of PCa vs. healthy controls. This systematic review aims to investigate and compare the microbiome of PCa and healthy tissue to determine the microbial association with the pathogenesis of PCa. We searched MEDLINE, Embase, and Scopus databases. Articles were screened by two independent and blinded reviewers. Literature that compared the prostatic tissue microbiome of patients with PCa with benign controls was included. We found that PCa may be associated with increased Propionibacterium acnes, the herpesviridae and papillomaviridae families, and Mycoplasma genitalium, but definitive conclusions cannot be drawn from the existing data. Challenges include the difficulty of obtaining uncontaminated tissue samples and securing tissue from healthy controls. As a result, methods are varied with many studies using cancerous and “healthy” tissue from the same prostate. The organisms chosen for each study were also highly variable, making it difficult to compare studies. These issues have led to lower confidence in our results. Overall, further work is warranted to better understand the implications of the prostatic microbiome in the pathogenesis of PCa. Full article

Epstein–Barr virus (EBV), a Herpesviridae family member, is associated with an increased risk of autoimmune disease development in the host. We previously demonstrated that EBV DNA elevates levels of the pro-inflammatory cytokine IL-17A and that inhibiting Toll-like receptor (TLR) 3, 7, or 9 reduces its levels. Moreover, this DNA exacerbated colitis in a mouse model of inflammatory bowel disease (IBD). In the study at hand, we examined whether inhibition of TLR3, 7, or 9 alleviates this exacerbation. Mice were fed 1.5% dextran sulfate sodium (DSS) water and administered EBV DNA. Then, they were treated with a TLR3, 7, or 9 inhibitor or left untreated. We also assessed the additive impact of combined inhibition of all three receptors. Mice that received DSS, EBV DNA, and each inhibitor alone, or a combination of inhibitors, showed significant improvement. They also had a decrease in the numbers of the pathogenic colonic IL-17A+IFN-γ+ foci. Inhibition of all three endosomal TLR receptors offered no additive benefit over administering a single inhibitor. Therefore, inhibition of endosomal TLRs reduces EBV DNA exacerbation of mouse colitis, offering a potential approach for managing IBD patients infected with EBV. Full article

Shortly after the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cases of viral, bacterial, and fungal coinfections in hospitalized patients became evident. This retrospective study investigates the prevalence of multiple pathogen co-detections in 1472 lower respiratory tract (LRT) samples from 229 SARS-CoV-2-positive patients treated in the largest intensive care unit (ICU) in Slovenia. In addition to SARS-CoV-2, (rt)RT-PCR tests were used to detect cytomegalovirus (CMV), Epstein–Barr virus (EBV), herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), varicella zoster virus (VZV), and atypical bacteria: Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila/spp. At least one co-detection was observed in 89.1% of patients. EBV, HSV-1, and CMV were the most common, with 74.7%, 58.1%, and 38.0% of positive patients, respectively. The median detection time of EBV, HSV-1, and CMV after initial SARS-CoV-2 confirmation was 11 to 20 days. Bronchoalveolar lavage (BAL) and tracheal aspirate (TA) samples showed equivalent performance for the detection of EBV, CMV, and HSV-1 in patients with both available samples. Our results indicate that SARS-CoV-2 infection could be a risk factor for latent herpesvirus reactivation, especially HSV-1, EBV, and CMV. However, additional studies are needed to elucidate the clinical importance of these findings. Full article

Pseudorabies is an acute and febrile infectious disease caused by pseudorabies virus (PRV), a member of the family Herpesviridae. Currently, PRV is predominantly endemoepidemic and has caused significant economic losses among domestic pigs. Other animals have been proven to be susceptible to PRV, with a mortality rate of 100%. In addition, 30 human cases of PRV infection have been reported in China since 2017, and all patients have shown severe neurological symptoms and eventually died or developed various neurological sequelae. In these cases, broad-spectrum anti-herpesvirus drugs and integrated treatments were mostly applied. However, the inhibitory effect of the commonly used anti-herpesvirus drugs (e.g., acyclovir, etc.) against PRV were evaluated and found to be limited in this study. It is therefore urgent and important to develop drugs that are clinically effective against PRV infection. Here, we constructed a high-throughput method for screening antiviral drugs based on fluorescence-tagged PRV strains and multi-modal microplate readers that detect fluorescence intensity to account for virus proliferation. A total of 2104 small molecule drugs approved by the U.S. Food and Drug Administration (FDA) were studied and validated by applying this screening model, and 104 drugs providing more than 75% inhibition of fluorescence intensity were selected. Furthermore, 10 drugs that could significantly inhibit PRV proliferation in vitro were strictly identified based on their cytopathic effects, virus titer, and viral gene expression, etc. Based on the determined 50% cytotoxic concentration (CC₅₀) and 50% inhibitory concentration (IC₅₀), the selectivity index (SI) was calculated to be 26.3–3937.2 for these 10 drugs, indicating excellent drugability. The antiviral effects of the 10 drugs were then assessed in a mouse model. It was found that 10 mg/kg brincidofovir administered continuously for 5 days provided 100% protection in mice challenged with lethal doses of the human-origin PRV strain hSD-1/2019. Brincidofovir significantly attenuated symptoms and pathological changes in infected mice. Additionally, time-of-addition experiments confirmed that brincidofovir inhibited the proliferation of PRV mainly by interfering with the viral replication stage. Therefore, this study confirms that brincidofovir can significantly inhibit PRV both in vitro and in vivo and is expected to be an effective drug candidate for the clinical treatment of PRV infections. Full article

The rise of drug resistance to antivirals poses a significant global concern for public health; therefore, there is a pressing need to identify novel compounds that can effectively counteract strains resistant to current antiviral treatments. In light of this, researchers have been exploring new approaches, including the investigation of natural compounds as alternative sources for developing potent antiviral therapies. Thus, this work aimed to evaluate the antiviral properties of the organic-soluble fraction of a root exudate derived from the tomato plant Solanum lycopersicum in the context of herpesvirus infections. Our findings demonstrated that a root exudate from Solanum lycopersicum exhibits remarkable efficacy against prominent members of the family Herpesviridae, specifically herpes simplex virus type 1 (HSV-1) (EC₅₀ 25.57 µg/mL, SI > 15.64) and human cytomegalovirus (HCMV) (EC₅₀ 9.17 µg/mL, SI 32.28) by inhibiting a molecular event during the herpesvirus replication phase. Moreover, the phytochemical fingerprint of the Solanum lycopersicum root exudate was characterized through mass spectrometry. Overall, these data have unveiled a novel natural product with antiherpetic activity, presenting a promising and valuable alternative to existing drugs. Full article