scholarly journals HSV-1 and Endogenous Retroviruses as Risk Factors in Demyelination

2021 ◽  
Vol 22 (11) ◽  
pp. 5738
Author(s):  
Raquel Bello-Morales ◽  
Sabina Andreu ◽  
Inés Ripa ◽  
José Antonio López-Guerrero
Keyword(s):  
Risk Factor ◽  
Dna Sequences ◽  
Demyelinating Disease ◽  
Molecular Mimicry ◽  
Current Knowledge ◽  
Endogenous Retroviruses ◽  
Unknown Etiology ◽  
Genetic And Environmental Factors ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that can infect the peripheral and central nervous systems, and it has been implicated in demyelinating and neurodegenerative processes. Transposable elements (TEs) are DNA sequences that can move from one genomic location to another. TEs have been linked to several diseases affecting the central nervous system (CNS), including multiple sclerosis (MS), a demyelinating disease of unknown etiology influenced by genetic and environmental factors. Exogenous viral transactivators may activate certain retrotransposons or class I TEs. In this context, several herpesviruses have been linked to MS, and one of them, HSV-1, might act as a risk factor by mediating processes such as molecular mimicry, remyelination, and activity of endogenous retroviruses (ERVs). Several herpesviruses have been involved in the regulation of human ERVs (HERVs), and HSV-1 in particular can modulate HERVs in cells involved in MS pathogenesis. This review exposes current knowledge about the relationship between HSV-1 and human ERVs, focusing on their contribution as a risk factor for MS.

scholarly journals The Role of Herpes Simplex Virus Type 1 Infection in Demyelination of the Central Nervous System

2020 ◽  
Vol 21 (14) ◽  
pp. 5026 ◽  
Author(s):  
Raquel Bello-Morales ◽  
Sabina Andreu ◽  
José Antonio López-Guerrero
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex ◽  
Molecular Mimicry ◽  
Current Knowledge ◽  
Endogenous Retroviruses ◽  
Surrounding Tissue ◽  
The Central Nervous System ◽  
Hsv 1

Herpes simplex type 1 (HSV-1) is a neurotropic virus that infects the peripheral and central nervous systems. After primary infection in epithelial cells, HSV-1 spreads retrogradely to the peripheral nervous system (PNS), where it establishes a latent infection in the trigeminal ganglia (TG). The virus can reactivate from the latent state, traveling anterogradely along the axon and replicating in the local surrounding tissue. Occasionally, HSV-1 may spread trans-synaptically from the TG to the brainstem, from where it may disseminate to higher areas of the central nervous system (CNS). It is not completely understood how HSV-1 reaches the CNS, although the most accepted idea is retrograde transport through the trigeminal or olfactory tracts. Once in the CNS, HSV-1 may induce demyelination, either as a direct trigger or as a risk factor, modulating processes such as remyelination, regulation of endogenous retroviruses, or molecular mimicry. In this review, we describe the current knowledge about the involvement of HSV-1 in demyelination, describing the pathways used by this herpesvirus to spread throughout the CNS and discussing the data that suggest its implication in demyelinating processes.

Transcriptional control signals of a herpes simplex virus type 1 late (gamma 2) gene lie within bases -34 to +124 relative to the 5' terminus of the mRNA

1986 ◽  
Vol 6 (11) ◽  
pp. 3652-3666
Author(s):  
F L Homa ◽  
T M Otal ◽  
J C Glorioso ◽  
M Levine
Keyword(s):  
Herpes Simplex ◽  
Dna Sequences ◽  
Viral Dna ◽  
Regulated Expression ◽  
Base Pair Fragment ◽  
Simplex Virus ◽  
Pair Fragment ◽  
Gc Gene ◽  
Hsv 1

The cis-acting DNA sequences required for regulated expression of a herpes simplex virus type 1 (HSV-1) late (gamma 2) gene were studied by using viruses containing specific deletions in the 5' transcribed noncoding and upstream regions of the HSV-1 glycoprotein C (gC) gene, a model gamma 2 gene. Nine mutant viruses which had variable 5' and 3' deletions within bases -569 to +124 relative to the 5' terminus of the gC mRNA were isolated. The mutants were isolated by a simple in situ hybridization screening procedure not requiring any prior selective pressure for or against expression of the gC gene. Analysis of RNA extracted from cells infected with individual mutants showed that the DNA sequences required for regulated expression of this gamma 2 gene lay within bases -34 to +124. This 158-base-pair fragment was sufficient to confer accurate and quantitative expression of gC mRNA and to maintain the stringent requirement on viral DNA replication for expression of this gene. Moreover, it was found that sequences located between -34 and +14 contained signals essential for expression of gC. To determine whether the -34 to +124 sequences would function as a gamma 2 promoter when moved to another region of the HSV-1 genome, the 158-base-pair fragment was substituted for the normal thymidine kinase promoter-regulatory sequences in the thymidine-kinase gene locus. Transcription of this chimeric gene was regulated as a gamma 2 gene in that its expression in infected cells was dependent on viral DNA synthesis. The only recognizable consensus sequence upstream of the transcription initiation site for this gene was the TATAAA sequence at -30.

Cross-talk of the environment with the host genome and the immune system through endogenous retroviruses in systemic lupus erythematosus

Lupus ◽  
2009 ◽  
Vol 18 (13) ◽  
pp. 1136-1143 ◽  
Author(s):  
M. Blank ◽  
Y. Shoenfeld ◽  
A. Perl
Keyword(s):  
Lupus Erythematosus ◽  
Molecular Mimicry ◽  
Current Knowledge ◽  
Stress Hormones ◽  
Cross Reactivity ◽  
Histone Deacetylation ◽  
Endogenous Retroviruses ◽  
Autoimmune Response ◽  
Human Endogenous Retroviruses ◽  
Ultraviolet Exposure

Environmental factors are capable of triggering the expression of human endogenous retroviruses and induce an autoimmune response. Infection can promote the expression of human endogenous retroviruses by molecular mimicry or by functional mimicry. There are additional mechanisms which may control the expression of human endogenous retroviruses, such as epigenetic status of the genome (hypomethylation, histone deacetylation). Ultraviolet exposure, chemicals/drugs, injury/stress, hormones, all as a single cause or in a concert, may modulate the involvement of human endogenous retroviruses in pathogenic processes. In the current review we summarize the current knowledge on infections, molecular mimicry, cross-reactivity and epigenetics contribution for trigger human endogenous retroviruses expression and pathogenesis in lupus patients. Lupus (2009) 18, 1136—1143.

scholarly journals Transcriptional control signals of a herpes simplex virus type 1 late (gamma 2) gene lie within bases -34 to +124 relative to the 5' terminus of the mRNA.

1986 ◽  
Vol 6 (11) ◽  
pp. 3652-3666 ◽  
Author(s):  
F L Homa ◽  
T M Otal ◽  
J C Glorioso ◽  
M Levine
Keyword(s):  
Herpes Simplex ◽  
Dna Sequences ◽  
Viral Dna ◽  
Regulated Expression ◽  
Base Pair Fragment ◽  
Simplex Virus ◽  
Pair Fragment ◽  
Gc Gene ◽  
Hsv 1

The cis-acting DNA sequences required for regulated expression of a herpes simplex virus type 1 (HSV-1) late (gamma 2) gene were studied by using viruses containing specific deletions in the 5' transcribed noncoding and upstream regions of the HSV-1 glycoprotein C (gC) gene, a model gamma 2 gene. Nine mutant viruses which had variable 5' and 3' deletions within bases -569 to +124 relative to the 5' terminus of the gC mRNA were isolated. The mutants were isolated by a simple in situ hybridization screening procedure not requiring any prior selective pressure for or against expression of the gC gene. Analysis of RNA extracted from cells infected with individual mutants showed that the DNA sequences required for regulated expression of this gamma 2 gene lay within bases -34 to +124. This 158-base-pair fragment was sufficient to confer accurate and quantitative expression of gC mRNA and to maintain the stringent requirement on viral DNA replication for expression of this gene. Moreover, it was found that sequences located between -34 and +14 contained signals essential for expression of gC. To determine whether the -34 to +124 sequences would function as a gamma 2 promoter when moved to another region of the HSV-1 genome, the 158-base-pair fragment was substituted for the normal thymidine kinase promoter-regulatory sequences in the thymidine-kinase gene locus. Transcription of this chimeric gene was regulated as a gamma 2 gene in that its expression in infected cells was dependent on viral DNA synthesis. The only recognizable consensus sequence upstream of the transcription initiation site for this gene was the TATAAA sequence at -30.

scholarly journals Achalasia—An Autoimmune Inflammatory Disease: A Cross-Sectional Study

2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
J. Furuzawa-Carballeda ◽  
D. Aguilar-León ◽  
A. Gamboa-Domínguez ◽  
M. A. Valdovinos ◽  
C. Nuñez-Álvarez ◽  
...  
Keyword(s):  
Cross Sectional Study ◽  
Unknown Etiology ◽  
Histopathological Analysis ◽  
Sphincter Muscle ◽  
Herpes Simplex Virus 1 ◽  
Cross Sectional ◽  
High Resolution Manometry ◽  
Simplex Virus ◽  
Type Iii Achalasia ◽  
Hsv 1

Idiopathic achalasia is a disease of unknown etiology. The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism. Thirty-two patients diagnosed by high-resolution manometry with achalasia were included. Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control). Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed. Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence. Herpes simplex virus-1 (HSV-1) infection was determined byin situhybridization, RT-PCR, and immunohistochemistry. Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%). Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregsversuscontrols (P<0.001). Circulating Th22/Th17/Th2/Th1 percentage showed a significant increaseversushealthy donors (P<0.01). Type III achalasia patients exhibited the highest inflammatory responseversustypes I and II. Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100%versus0% in controls. Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection.

scholarly journals Herpes Simplex Virus 1 Gene Products Occlude the Interferon Signaling Pathway at Multiple Sites

2004 ◽  
Vol 78 (8) ◽  
pp. 4185-4196 ◽  
Author(s):  
Ana Virginia Chee ◽  
Bernard Roizman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Signaling Pathway ◽  
Dna Sequences ◽  
Interferon Response ◽  
Interferon Signaling ◽  
Herpes Simplex Virus 1 ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Earlier studies have shown that herpes simplex virus 1 (HSV-1) blocks the interferon response pathways, at least at two sites, by circumventing the effects of activation of protein kinase R by double-stranded RNA and interferon and through the degradation of promyelocytic leukemia protein (PML) since interferon has no antiviral effects in PML−/− cells. Here we report on two effects of viral genes on other sites of the interferon signaling pathway. (i) In infected cells, Jak1 kinase associated with interferon receptors and Stat2 associated with the interferon signaling pathway rapidly disappear from infected cells. The level of interferon alpha receptor is also reduced, albeit less drastically at times after 4 h postinfection. Other members of the Stat family of proteins were either decreased in amount or posttranslationally processed in a manner different from those of mock-infected cells. The decrease in the levels of Jak1 and Stat2 may account for the decrease in the formation of complexes consisting of Stat1 or ISGF3 and DNA sequences containing the interferon-stimulated response elements after exposure to interferon. (ii) The disappearance of Jak1 and Stat2 was related at least in part to the function of the virion host shutoff protein, the product of the viral UL41 gene. Consistent with this observation, a mutant lacking the UL41 gene and treated with interferon produced lesser amounts of a late protein (UL38) than the wild-type parent. We conclude that HSV-1 blocks the interferon signaling pathways at several sites.

scholarly journals Herpes Simplex Virus Type 1 in the Brain, Apolipoprotein E Genotype and Alzheimer’s Disease

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Uwe Beffert ◽  
Philippe Bertrand ◽  
Danielle Champagne ◽  
Serge Gauthier ◽  
Judes Poirier
Keyword(s):  
Risk Factor ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Type ◽  
Brain Regions ◽  
Ε4 Allele ◽  
Simplex Virus ◽  
The Brain ◽  
Hsv 1

The ε4 allele of apolipoprotein E (apoE) is an important risk factor for Alzheimer's disease (AD), however, it is not required nor sufficient to cause the disease on its own. Herpes viruses cause acute and chronic diseases of the central nervous system and have been implicated in AD. Using a sensitive polymerase chain reaction method, latent herpes simplex virus type 1 (HSV-1) has been detected from five different brain regions (hippocampus, frontal cortex, occipital cortex, cerebellum and striatum) of neuropathologically confirmed AD and control tissue. HSV-1 positivity was then correlated with AD, presence of the virus in specific brain regions, and apoE genotype. The results confirm that the ε4 allele of apoE is a risk factor for AD, while HSV-1 alone is not. This held true for all five brain regions examined. Furthermore, no synergy between the two factors could be found when any one of the brain regions was examined individually or when the data were pooled. These findings emphasize that the ε4 allele of apoE is a risk factor for AD and that HSV-1, either alone or in combination with apoE, does not represent an increased risk for AD. Furthermore, no particular brain region seems to be more infected with HSV-1 than another, even in those regions most affected in AD.

Assembly of VP26 in herpes simplex virus-1 capsid implicated by 3-D structure of recombinant capsid

1995 ◽  
Vol 53 ◽  
pp. 840-841
Author(s):  
Z. Hong Zhou ◽  
Jing He ◽  
Joanita Jakana ◽  
J. D. Tatman ◽  
Frazer J. Rixon ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
3D Structure ◽  
Structure Study ◽  
Herpes Simplex Virus 1 ◽  
Shell Proteins ◽  
Life Threatening ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus-1 (HSV-1) is a ubiquitous virus which is implicated in diseases ranging from self-curing cold sores to life-threatening infections. The 2500 Å diameter herpes virion is composed of a glycoprotein spike containing, lipid envelope, enclosing a protein layer (the tegument) in which is embedded the capsid (which contains the dsDNA genome). The B-, and A- and C-capsids, representing different morphogenetic stages in HSV-1 infected cells, are composed of 7, and 5 structural proteins respectively. The three capsid types are organized in similar T=16 icosahedral shells with 12 pentons, 150 hexons, and 320 connecting triplexes. Our previous 3D structure study at 26 Å revealed domain features of all these structural components and suggested probable locations for the outer shell proteins, VP5, VP26, VP19c and VP23. VP5 makes up most of both pentons and hexons. VP26 appeared to bind to the VP5 subunit in hexon but not to that in penton.

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