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Viruses Nov 2023Alpha herpesvirus infections (α-HVs) are widespread, affecting more than 70% of the adult human population. Typically, the infections start in the mucosal epithelia,... (Review)
Review
Alpha herpesvirus infections (α-HVs) are widespread, affecting more than 70% of the adult human population. Typically, the infections start in the mucosal epithelia, from which the viral particles invade the axons of the peripheral nervous system. In the nuclei of the peripheral ganglia, α-HVs establish a lifelong latency and eventually undergo multiple reactivation cycles. Upon reactivation, viral progeny can move into the nerves, back out toward the periphery where they entered the organism, or they can move toward the central nervous system (CNS). This latency-reactivation cycle is remarkably well controlled by the intricate actions of the intrinsic and innate immune responses of the host, and finely counteracted by the viral proteins in an effort to co-exist in the population. If this yin-yang- or Nash-equilibrium-like balance state is broken due to immune suppression or genetic mutations in the host response factors particularly in the CNS, or the presence of other pathogenic stimuli, α-HV reactivations might lead to life-threatening pathologies. In this review, we will summarize the molecular virus-host interactions starting from mucosal epithelia infections leading to the establishment of latency in the PNS and to possible CNS invasion by α-HVs, highlighting the pathologies associated with uncontrolled virus replication in the NS.
Topics: Humans; Virus Latency; Alphaherpesvirinae; Axons; Virus Replication; Viral Proteins
PubMed: 38140525
DOI: 10.3390/v15122284 -
Journal of Neuroinflammation Jun 2023Trigeminal ganglia (TG) neurons are an important site of lifelong latent varicella-zoster virus (VZV) infection. Although VZV-specific T-cells are considered pivotal to...
BACKGROUND
Trigeminal ganglia (TG) neurons are an important site of lifelong latent varicella-zoster virus (VZV) infection. Although VZV-specific T-cells are considered pivotal to control virus reactivation, their protective role at the site of latency remains uncharacterized.
METHODS
Paired blood and TG specimens were obtained from ten latent VZV-infected adults, of which nine were co-infected with herpes simplex virus type 1 (HSV-1). Short-term TG-derived T-cell lines (TG-TCL), generated by mitogenic stimulation of TG-derived T-cells, were probed for HSV-1- and VZV-specific T-cells using flow cytometry. We also performed VZV proteome-wide screening of TG-TCL to determine the fine antigenic specificity of VZV reactive T-cells. Finally, the relationship between T-cells and latent HSV-1 and VZV infections in TG was analyzed by reverse transcription quantitative PCR (RT-qPCR) and in situ analysis for T-cell proteins and latent viral transcripts.
RESULTS
VZV proteome-wide analysis of ten TG-TCL identified two VZV antigens recognized by CD8 T-cells in two separate subjects. The first was an HSV-1/VZV cross-reactive CD8 T-cell epitope, whereas the second TG harbored CD8 T-cells reactive with VZV specifically and not the homologous peptide in HSV-1. In silico analysis showed that HSV-1/VZV cross reactivity of TG-derived CD8 T-cells reactive with ten previously identified HSV-1 epitopes was unlikely, suggesting that HSV-1/VZV cross-reactive T-cells are not a common feature in dually infected TG. Finally, no association was detected between T-cell infiltration and VZV latency transcript abundance in TG by RT-qPCR or in situ analyses.
CONCLUSIONS
The low presence of VZV- compared to HSV-1-specific CD8 T-cells in human TG suggests that VZV reactive CD8 T-cells play a limited role in maintaining VZV latency.
Topics: Adult; Humans; Proteome; Herpesvirus 3, Human; Prevalence; Trigeminal Ganglion; CD8-Positive T-Lymphocytes; Epitopes; Herpesvirus 1, Human
PubMed: 37308917
DOI: 10.1186/s12974-023-02820-y -
Archives of Virology Feb 2021We present the complete genome sequence of bovine alphaherpesvirus 2 (BoHV-2), a member of the family Herpesviridae, subfamily Alphaherpesvirinae, genus Simplexvirus....
We present the complete genome sequence of bovine alphaherpesvirus 2 (BoHV-2), a member of the family Herpesviridae, subfamily Alphaherpesvirinae, genus Simplexvirus. BoHV-2 is the causative agent of bovine ulcerative mammillitis (bovine herpes mammillitis) and pseudo-lumpy skin disease. The genomic architecture of BoHV-2 is typical of most simplexvirus genomes and congruent with that of human alphaherpesvirus 1 (HHV-1). The genome comprises a total of 131,245 base pairs and has an overall G+C content of 64.9 mol%. A total of 75 open reading frames are predicted. The gene repertoire of BoHV-2 is analogous to that of HHV-1, although the coding region of US12 is missing. A phylogenetic analysis supported BoHV-2 as a member of the genus Simplexvirus.
Topics: Animals; Base Composition; Cattle; Cattle Diseases; DNA, Viral; Genome, Viral; Herpesvirus 1, Bovine; Herpesvirus 2, Bovine; Open Reading Frames; Phylogeny
PubMed: 33315144
DOI: 10.1007/s00705-020-04895-x -
Scientific Reports Mar 2021It is uncertain whether clinical severity of an infection varies by pathogen or by multiple infections. Using hospital-based surveillance in children, we investigate the...
It is uncertain whether clinical severity of an infection varies by pathogen or by multiple infections. Using hospital-based surveillance in children, we investigate the range of clinical severity for patients singly, multiply, and not infected with a group of commonly circulating viruses in Nha Trang, Vietnam. RT-PCR was performed to detect 13 respiratory viruses in nasopharyngeal samples from enrolled patients. We apply a novel clinical severity score and examine associations with the odds of being severe and differences in raw severity scores. We find no difference in severity between 0-, 1-, and 2-concurrent infections and little differences in severity between specific viruses. We find RSV and HMPV infections to be associated with 2- and 1.5-fold increase in odds of being severe, respectively, and that infection with ADV is consistently associated with lower risk of severity. Clinically, based on the results here, if RSV or HMPV virus is suspected, PCR testing for confirmatory diagnosis and for detection of multiple coinfecting viruses would be fruitful to assess whether a patient's disease course is going to be severe.
Topics: Alphaherpesvirinae; Child; Child, Hospitalized; Child, Preschool; Coinfection; Female; Humans; Infant; Infant, Newborn; Male; Metapneumovirus; Nasopharynx; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Vietnam; Virus Diseases
PubMed: 33664311
DOI: 10.1038/s41598-021-84423-2 -
Biochimica Et Biophysica Acta 2010The immediate early genes of the alpha-herpesviruses HSV and VZV are transcriptionally regulated by viral and cellular factors in a complex combinatorial manner. Despite... (Review)
Review
The immediate early genes of the alpha-herpesviruses HSV and VZV are transcriptionally regulated by viral and cellular factors in a complex combinatorial manner. Despite this complexity and the apparent redundancy of activators, the expression of the viral IE genes is critically dependent upon the cellular transcriptional coactivator HCF-1. Although the role of HCF-1 had remained elusive, recent studies have demonstrated that the protein is a component of multiple chromatin modification complexes including the Set1/MLL1 histone H3K4 methyltransferases. Studies using model viral promoter-reporter systems as well as analyses of components recruited to the viral genome during the initiation of infection have elucidated the significance of HCF-1 chromatin modification complexes in contributing to the final state of modified histones assembled on the viral IE promoters. Strikingly, the absence of HCF-1 results in the accumulation of nucleosomes bearing repressive marks on the viral IE promoters and silencing of viral gene expression.
Topics: Alphaherpesvirinae; Chromatin; DNA Methylation; Gene Expression Regulation, Viral; Genes, Immediate-Early; Histones; Host Cell Factor C1; Humans; Transcription, Genetic
PubMed: 19682612
DOI: 10.1016/j.bbagrm.2009.08.003 -
Methods in Molecular Biology (Clifton,... 2022The development of compartmentalized neuron culture systems has been invaluable in the study of neuroinvasive viruses, including the alpha herpesviruses Herpes Simplex...
The development of compartmentalized neuron culture systems has been invaluable in the study of neuroinvasive viruses, including the alpha herpesviruses Herpes Simplex Virus 1 (HSV-1) and Pseudorabies Virus (PRV). This chapter provides updated protocols for assembling and culturing rodent embryonic superior cervical ganglion (SCG) and dorsal root ganglion (DRG) neurons in Campenot trichamber cultures. In addition, we provide several illustrative examples of the types of experiments that are enabled by Campenot cultures: (1) Using fluorescence microscopy to investigate axonal outgrowth/extension through the chambers, and alpha herpesvirus infection, intracellular trafficking, and cell-cell spread via axons. (2) Using correlative fluorescence microscopy and cryo electron tomography to investigate the ultrastructure of virus particles trafficking in axons.
Topics: Animals; Axonal Transport; Axons; Herpesvirus 1, Human; Herpesvirus 1, Suid; Neurons
PubMed: 35412277
DOI: 10.1007/978-1-0716-1990-2_9 -
Virology Journal Oct 2011Herpes simplex virus (HSV) type-1 and type-2 have evolved numerous strategies to infect a wide range of hosts and cell types. The result is a very successful prevalence... (Review)
Review
Herpes simplex virus (HSV) type-1 and type-2 have evolved numerous strategies to infect a wide range of hosts and cell types. The result is a very successful prevalence of the virus in the human population infecting 40-80% of people worldwide. HSV entry into host cell is a multistep process that involves the interaction of the viral glycoproteins with various cell surface receptors. Based on the cell type, HSV enter into host cell using different modes of entry. The combination of various receptors and entry modes has resulted in a virus that is capable of infecting virtually all cell types. Identifying the common rate limiting steps of the infection may help the development of antiviral agents that are capable of preventing the virus entry into host cell. In this review we describe the major features of HSV entry that have contributed to the wide susceptibility of cells to HSV infection.
Topics: Host Specificity; Humans; Receptors, Virus; Simplexvirus; Viral Tropism; Virus Internalization
PubMed: 22029482
DOI: 10.1186/1743-422X-8-481 -
Viruses Dec 2022Herpesviruses have complex mechanisms enabling infection of the human CNS and evasion of the immune system, allowing for indefinite latency in the host. Herpesvirus...
Herpesviruses have complex mechanisms enabling infection of the human CNS and evasion of the immune system, allowing for indefinite latency in the host. Herpesvirus infections can cause severe complications of the central nervous system (CNS). Here, we provide a novel characterization of cerebrospinal fluid (CSF) proteomes from patients with meningitis or encephalitis caused by human herpes simplex virus 1 (HSV-1), which is the most prevalent human herpesvirus associated with the most severe morbidity. The CSF proteome was compared with those from patients with meningitis or encephalitis due to human herpes simplex virus 2 (HSV-2) or varicella-zoster virus (VZV, also known as human herpesvirus 3) infections. Virus-specific differences in CSF proteomes, most notably elevated 14-3-3 family proteins and calprotectin (i.e., S100-A8 and S100-A9), were observed in HSV-1 compared to HSV-2 and VZV samples, while metabolic pathways related to cellular and small molecule metabolism were downregulated in HSV-1 infection. Our analyses show the feasibility of developing CNS proteomic signatures of the host response in alpha herpes infections, which is paramount for targeted studies investigating the pathophysiology driving virus-associated neurological disorders, developing biomarkers of morbidity, and generating personalized therapeutic strategies.
Topics: Humans; Proteome; Proteomics; Herpesviridae Infections; Central Nervous System; Herpesvirus 3, Human; Herpesvirus 1, Human; Herpesvirus 2, Human; Meningitis; Encephalitis
PubMed: 36560759
DOI: 10.3390/v14122757 -
Molecular Cell Jul 2021DNA-induced liquid-liquid phase separation of cyclic GMP-AMP synthase (cGAS) triggers a potent response to detect pathogen infection and promote innate immune signaling....
DNA-induced liquid-liquid phase separation of cyclic GMP-AMP synthase (cGAS) triggers a potent response to detect pathogen infection and promote innate immune signaling. Whether and how pathogens manipulate cGAS-DNA condensation to mediate immune evasion is unknown. We report the identification of a structurally related viral tegument protein family, represented by ORF52 and VP22 from gamma- and alpha-herpesvirinae, respectively, that employs a conserved mechanism to restrict cGAS-DNA phase separation. ORF52/VP22 proteins accumulate into, and effectively disrupt, the pre-formed cGAS-DNA condensation both in vitro and in cells. The inhibition process is dependent on DNA-induced liquid-liquid phase separation of the viral protein rather than a direct interaction with cGAS. Moreover, highly abundant ORF52 proteins carried within viral particles are able to target cGAS-DNA phase separation in early infection stage. Our results define ORF52/VP22-type tegument proteins as a family of inhibitors targeting cGAS-DNA phase separation and demonstrate a mechanism for how viruses overcome innate immunity.
Topics: Alphaherpesvirinae; Betaherpesvirinae; DNA; HEK293 Cells; HeLa Cells; Herpesviridae Infections; Humans; Immune Evasion; Immunity, Innate; Nucleotidyltransferases; Viral Structural Proteins
PubMed: 34015248
DOI: 10.1016/j.molcel.2021.05.002 -
EcoHealth Jun 2021Fibropapillomatosis (FP) is a tumorigenic panzootic disease of sea turtles, most common in green turtles (Chelonia mydas). FP is linked to the chelonid alphaherpesvirus...
Fibropapillomatosis (FP) is a tumorigenic panzootic disease of sea turtles, most common in green turtles (Chelonia mydas). FP is linked to the chelonid alphaherpesvirus 5 (ChAHV5) and to degraded habitats and, though benign, large tumours can hinder vital functions, causing death. We analyse 108 green turtles, captured in 2018 and 2019, at key foraging grounds in Guinea-Bissau and Mauritania, West Africa, for the presence of FP, and use real-time PCR to detect ChAHV5 DNA, in 76 individuals. The prevalence of FP was moderate; 33% in Guinea-Bissau (n = 36) and 28% in Mauritania (n = 72), and most turtles were mildly affected, possibly due to low human impact at study locations. Juveniles had higher FP prevalence (35%, n = 82) compared to subadults (5%, n = 21), probably because individuals acquire resistance over time. ChAHV5 DNA was detected in 83% (n = 24) of the tumour biopsies, consistent with its role as aetiological agent of FP and in 26% (n = 27) of the 'normal' skin (not showing lesions) from FP turtles. Notably, 45% of the asymptomatic turtles were positive for ChAHV5, supporting multifactorial disease expression. We report the first baselines of FP and ChAHV5 prevalence for West Africa green turtles, essential to assess evolution of disease and future impacts of anthropogenic activities.
Topics: Africa, Western; Alphaherpesvirinae; Animals; DNA, Viral; Herpesviridae Infections; Prevalence; Skin Neoplasms; Turtles
PubMed: 34241724
DOI: 10.1007/s10393-021-01526-y