Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them?
Abstract
:1. Introduction
2. Neurodegenerative Diseases
2.1. Herpesviruses’ Role in the Pathogenesis of Neurodegenerative Diseases
2.2. Research Data That Establish a Link between AD and Herpesviruses
2.3. Research Data That Establish a Link between PD and Herpesviruses
3. Autoimmune Diseases
3.1. Herpesviruses’ Role in the Pathogenesis of Autoimmune Diseases
3.2. Research Data That Establish a Link between Multiple Sclerosis and Herpesviruses
3.2.1. Molecular Mimicry
3.2.2. Defective EBV Immune Responses
3.2.3. EBV Induced Inflammation
3.3. Research Data That Establish a Link between Systemic Lupus Erythematosus and Herpesviruses
3.4. Research Data That Establish a Link between Sjögren’s Syndrome and Herpesviruses
4. Relationship between Herpesviruses, Neurological Disorders and Autoimmune Diseases
5. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Disease | Result | Study Type | Refs |
---|---|---|---|
AD | The presence of Aβ and HSV-1 cross-reactive antibodies in patients with AD | Comparative study | [73] |
An increased level of IgM antibodies against HSV-1,2 was associated with an increased risk of developing dementia | Prospective cohort studies | [74,75] | |
AD-derived B lymphocytes infected with EBV produced high levels of TNF-α in vitro | Cell model studies | [78,79] | |
EBV antigens stimulated cytotoxic and proinflammatory functions by CD45RA+ cells | Prospective cohort and knockout studies | [80,81] | |
Increased CMV blood markers associated with cognitive decline | Longitudinal, prospective cohort studies | [76,100] | |
Levels of CMV IgG antibodies associated with increased neurofibrillary tangles | Longitudinal study | [101] | |
Patients with herpes zoster showed a significantly increased risk of developing AD | Retrospective cohort studies | [95,96] | |
Studies showed an association between CMV and moderate–severe dementia | Population cohort study | [99] | |
HSV-1 induced neuroinflammation | In vitro model studies | [47,48,49,50,51] | |
HSV-1 induced the production of both Aβ and the tau protein in human neural cells | In vitro infection studies | [55] | |
HSV-1 DNA was present in the brain of AD patients | Molecular studies | [57,58] | |
EBV was present in the blood and brains of AD patients | Comparative and molecular study | [76] | |
EBV reactivation has been associated with cognitive decline | Longitudinal study | [77] | |
EBV BNLF-2a has been associated with AD progression | Biochemical studies | [82,83] | |
HHV-6-infected microglia showed an accumulation of Aβ and tau proteins | In vivo and in vitro infection model | [85,86] | |
HHV-6 reduced autophagy | In vitro infection model | [87,88,89] | |
HHV-6-infected patients and AD patients shared 95 differentially expressed genes | Computational analysis study | [90] | |
Binding of VZV to the insulin-degrading enzyme | In vitro infection model | [97,98] | |
PD | Molecular mimicry between HSV-1 and α-synuclein | Seroprevalence study | [102] |
Molecular mimicry between EBV LMP1 and α-synuclein | Seroprevalence study | [104] | |
CMV-, EBV-, and HHV-6-infected patients shared several differentially expressed genes with AD patients | Computational analysis study | [90] |
Disease | Result | Study Type | Refs |
---|---|---|---|
MS | Molecular mimicry between HSV-1 protein and myelin basic protein | Biochemical study | [150] |
Molecular mimicry between EBV protein LMP-1 and different proteins involved in MS pathogenesis | Case–control studies | [152,153,154,155] | |
Molecular mimicry between EBV proteins BHRF1 and BPLF1 with a protein present in neurons | Epitope discover approach and cell immunity analysis | [158] | |
Defective cytotoxic T cells control of EBV in MS | Seroprevalence study | [159] | |
Oligoclonal IgG against EBV have been detected in the brain of MS patients | Comparative study | [161] | |
Higher titers of EBV antibodies have been detected in MS patients | Case control study | [164] | |
Serological response against HHV-6 was higher in MS patients | Molecular, case–control studies | [179,180,181,182,183] | |
Oligoclonal IgG against HHV-6 have been detected in the brains of MS patients | Seroprevalence study | [184] | |
Molecular mimicry between HHV-6 protein U24 and myelin basic protein | Seroprevalence study | [186] | |
Increased level of sCD46, the receptor for HHV-6 has been detected in MS patients | Immunological study | [193] | |
Molecular mimicry between HCMV antigen (UL86981-1003) and myelin oligodendrocyte glycoprotein (MOG) | In vivo experimental model | [199] | |
Patients with herpes zoster have been associated with a higher risk of MS | Population-based study and computational GWAS | [202,206] | |
HSV-1 DNA in the blood and in the brains of MS patients | Molecular studies | [138,139] | |
HSV-1 infection-induced CNS demyelination and neuroinflammation | In vitro and in vivo infection studies | [140,141,142,143,145] | |
EBV-induced an inflammatory environment | In vitro infection and molecular studies | [168,169,170,171,172,173] | |
High load of HCMV genome has been detected in MS patients | Case–control study | [195] | |
High load of VZV genome has been detected in MS patients | Molecular study | [205] | |
SLE | Serological response against EBV was higher in SLE patients | Case–control studies | [209,210,211] |
EBV antibodies cross-reacted with autoantigens of SLE | Seroprevalence studies | [215,216,217] | |
Similarity between CMV antigens and autoantigens of SLE | Animal model and in vitro infection studies | [222,223] | |
High load of EBV DNA was detected in SLE patients | Molecular study | [207] | |
vIL-10, a viral EBV protein, has been detected at higher concentrations in plasma of SLE patients | In vitro infection model | [219] | |
SS | Higher titers of anti-HHV-6 have been found in a group of SS patients | Seroprevalence study | [235] |
A significant correlation between herpes zoster exposure and SS risk has been detected | Population-based case–control study | [234] | |
High levels of EBV DNA have been detected in SS patients | Molecular study | [230] | |
Increased EBV reactivation has been observed in SS patients | Observational study | [228] |
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De Francesco, M.A. Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them? Viruses 2024, 16, 133. https://doi.org/10.3390/v16010133
De Francesco MA. Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them? Viruses. 2024; 16(1):133. https://doi.org/10.3390/v16010133
Chicago/Turabian StyleDe Francesco, Maria Antonia. 2024. "Herpesviridae, Neurodegenerative Disorders and Autoimmune Diseases: What Is the Relationship between Them?" Viruses 16, no. 1: 133. https://doi.org/10.3390/v16010133