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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 -
Neoplasia (New York, N.Y.) Nov 1999The design of effective gene therapy strategies for brain tumors and other neurological disorders relies on the understanding of genetic and pathophysiological... (Review)
Review
The design of effective gene therapy strategies for brain tumors and other neurological disorders relies on the understanding of genetic and pathophysiological alterations associated with the disease, on the biological characteristics of the target tissue, and on the development of safe vectors and expression systems to achieve efficient, targeted and regulated, therapeutic gene expression. The herpes simplex virus type 1 (HSV-1) virion is one of the most efficient of all current gene transfer vehicles with regard to nuclear gene delivery in central nervous system-derived cells including brain tumors. HSV-1-related research over the past decades has provided excellent insight into the structure and function of this virus, which, in turn, facilitated the design of innovative vector systems. Here, we review aspects of HSV-1 structure, replication and pathogenesis, which are relevant for the engineering of HSV-1-based vectors.
Topics: Brain Neoplasms; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Herpesvirus 1, Human; Humans; Models, Biological; Nervous System Diseases
PubMed: 10933054
DOI: 10.1038/sj.neo.7900055 -
The Journal of General Virology Apr 2010Varicella-zoster virus (VZV), the cause of chickenpox and zoster, was the first human herpesvirus to be sequenced fully and the first for which vaccines have been... (Review)
Review
A proposal for a common nomenclature for viral clades that form the species varicella-zoster virus: summary of VZV Nomenclature Meeting 2008, Barts and the London School of Medicine and Dentistry, 24-25 July 2008.
Varicella-zoster virus (VZV), the cause of chickenpox and zoster, was the first human herpesvirus to be sequenced fully and the first for which vaccines have been licensed and widely used. Three groups have published genotyping schemes based on single nucleotide polymorphisms (SNPs) and, between them, have identified five distinct phylogenetic clades, with an additional two putative clades. Sequencing of over 23 whole VZV genomes from around the world further refined the phylogenetic distinctions between SNP genotypes. Widespread surveillance in countries in which the varicella vaccine is now in use and the difficulties posed by three unique genotyping approaches prompted an international meeting, at which a common nomenclature based on phylogenetic clades was agreed upon. In this paper, we review the original genotyping schemes and discuss the basis for a novel common nomenclature for VZV strains. We propose a minimum set of SNPs that we recommend should be used to genotype these viruses. Finally, we suggest criteria by which novel clades can be recognized.
Topics: Genome, Viral; Genotype; Herpesvirus 3, Human; Humans; Phylogeny; Polymorphism, Single Nucleotide; Terminology as Topic
PubMed: 20071486
DOI: 10.1099/vir.0.017814-0 -
Indian Journal of Ophthalmology Jul 2019
Topics: Herpesvirus 1, Human; Herpesvirus 3, Human; Humans; India; Keratitis, Herpetic; Real-Time Polymerase Chain Reaction
PubMed: 31238405
DOI: 10.4103/ijo.IJO_396_19 -
MBio Jun 2016Many molecular and cell biological details of the alphaherpesvirus assembly and egress pathway remain unclear. Recently we developed a live-cell fluorescence microscopy...
UNLABELLED
Many molecular and cell biological details of the alphaherpesvirus assembly and egress pathway remain unclear. Recently we developed a live-cell fluorescence microscopy assay of pseudorabies virus (PRV) exocytosis, based on total internal reflection fluorescence (TIRF) microscopy and a virus-encoded pH-sensitive fluorescent probe. Here, we use this assay to distinguish three classes of viral exocytosis in a nonpolarized cell type: (i) trafficking of viral glycoproteins to the plasma membrane, (ii) exocytosis of viral light particles, and (iii) exocytosis of virions. We find that viral glycoproteins traffic to the cell surface in association with constitutive secretory Rab GTPases and exhibit free diffusion into the plasma membrane after exocytosis. Similarly, both virions and light particles use these same constitutive secretory mechanisms for egress from infected cells. Furthermore, we show that viral light particles are distinct from cellular exosomes. Together, these observations shed light on viral glycoprotein trafficking steps that precede virus particle assembly and reinforce the idea that virions and light particles share a biogenesis and trafficking pathway.
IMPORTANCE
The alphaherpesviruses, including the important human pathogens herpes simplex virus 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), are among the few viruses that have evolved to exploit the mammalian nervous system. These viruses typically cause mild recurrent herpetic or zosteriform lesions but can also cause debilitating herpes encephalitis, more frequently in very young, old, immunocompromised, or nonnatural hosts. Importantly, many of the molecular and cellular mechanisms of viral assembly and egress remain unclear. This study addresses the trafficking of viral glycoproteins to the plasma membrane, exocytosis of light particles, and exocytosis of virions. Trafficking of glycoproteins affects immune evasion and pathogenesis and may precede virus particle assembly. The release of light particles may also contribute to immune evasion and pathogenesis. Finally, exocytosis of virions is important to understand, as this final step in the virus replication cycle produces infectious extracellular particles capable of spreading to the next round of host cells.
Topics: Animals; Biological Transport; Cell Line; Cell Membrane; Exocytosis; Fluorescent Dyes; Glycoproteins; Herpesvirus 1, Human; Herpesvirus 1, Suid; Herpesvirus 2, Human; Humans; Hydrogen-Ion Concentration; Immune Evasion; Microscopy, Fluorescence; Protein Transport; Sus scrofa; Viral Envelope Proteins; Virion; Virus Assembly; rab GTP-Binding Proteins
PubMed: 27273828
DOI: 10.1128/mBio.00820-16 -
Viruses Jun 2020Herpesviruses uniquely express two essential nuclear egress-regulating proteins forming a heterodimeric nuclear egress complex (core NEC). These core NECs serve as... (Review)
Review
Herpesviruses uniquely express two essential nuclear egress-regulating proteins forming a heterodimeric nuclear egress complex (core NEC). These core NECs serve as hexameric lattice-structured platforms for capsid docking and recruit viral and cellular NEC-associated factors that jointly exert nuclear lamina as well as membrane-rearranging functions (multicomponent NEC). The regulation of nuclear egress has been profoundly analyzed for murine and human cytomegaloviruses (CMVs) on a mechanistic basis, followed by the description of core NEC crystal structures, first for HCMV, then HSV-1, PRV and EBV. Interestingly, the highly conserved structural domains of these proteins stand in contrast to a very limited sequence conservation of the key amino acids within core NEC-binding interfaces. Even more surprising, although a high functional consistency was found when regarding the basic role of NECs in nuclear egress, a clear specification was identified regarding the limited, subfamily-spanning binding properties of core NEC pairs and NEC multicomponent proteins. This review summarizes the evolving picture of the relationship between sequence coevolution, structural conservation and properties of NEC interaction, comparing HCMV to α-, β- and γ-herpesviruses. Since NECs represent substantially important elements of herpesviral replication that are considered as drug-accessible targets, their putative translational use for antiviral strategies is discussed.
Topics: Active Transport, Cell Nucleus; Alphaherpesvirinae; Amino Acid Sequence; Capsid; Capsid Proteins; Cytomegalovirus; Gammaherpesvirinae; Humans; Nuclear Envelope; Nuclear Lamina; Virus Release
PubMed: 32599939
DOI: 10.3390/v12060683 -
The Journal of Investigative Dermatology Jan 2018Herpes simplex virus type 2 (HSV-2) is the causative agent of genital herpes. Matsuzawa et al have demonstrated that, in a mouse model, HSV-2 pathology is influenced by...
Herpes simplex virus type 2 (HSV-2) is the causative agent of genital herpes. Matsuzawa et al have demonstrated that, in a mouse model, HSV-2 pathology is influenced by the time infection occurs. Increased expression of the HSV-2 receptor Nectin-1 under the control of CLOCK coincided with an increase in viral titer suggesting that HSV-2 infection is regulated by the host circadian clock.
Topics: Animals; Cell Adhesion Molecules; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Mice; Nectins; Virus Internalization
PubMed: 29273146
DOI: 10.1016/j.jid.2017.08.028 -
Journal of Virology Dec 2022Cyclic GMP-AMP synthase (cGAS), a key DNA sensor, detects cytosolic viral DNA and activates the adaptor protein stimulator of interferon genes (STING) to initiate...
Cyclic GMP-AMP synthase (cGAS), a key DNA sensor, detects cytosolic viral DNA and activates the adaptor protein stimulator of interferon genes (STING) to initiate interferon (IFN) production and host innate antiviral responses. Duck enteritis virus (DEV) is a duck alphaherpesvirus that causes an acute and contagious disease with high mortality in waterfowl. In the present study, we found that DEV inhibits host innate immune responses during the late phase of viral infection. Furthermore, we screened DEV proteins for their ability to inhibit the cGAS-STING DNA-sensing pathway and identified multiple viral proteins, including UL41, US3, UL28, UL53, and UL24, which block IFN-β activation through this pathway. The DEV tegument protein UL41, which exhibited the strongest inhibitory effect, selectively downregulated the expression of interferon regulatory factor 7 (IRF7) by reducing its mRNA accumulation, thereby inhibiting the DNA-sensing pathway. Ectopic expression of UL41 markedly reduced viral DNA-triggered IFN-β production and promoted viral replication, whereas deficiency of UL41 in the context of DEV infection increased the IFN-β response to DEV and suppressed viral replication. In addition, ectopic expression of IRF7 inhibited the replication of the UL41-deficient virus, whereas IRF7 knockdown facilitated its replication. This study is the first report identifying multiple viral proteins encoded by a duck DNA virus, which inhibit the cGAS-STING DNA-sensing pathway. These findings expand our knowledge of DNA sensing in ducks and reveal a mechanism through which DEV antagonizes the host innate immune response. Duck enteritis virus (DEV) is a duck alphaherpesvirus that causes an acute and contagious disease with high mortality, resulting in substantial economic losses in the commercial waterfowl industry. The evasion of DNA-sensing pathway-mediated antiviral innate immunity is essential for the persistent infection and replication of many DNA viruses. However, the mechanisms used by DEV to modulate the DNA-sensing pathway remain poorly understood. In the present study, we found that DEV encodes multiple viral proteins to inhibit the cGAS-STING DNA-sensing pathway. The DEV tegument protein UL41 selectively diminished the accumulation of interferon regulatory factor 7 (IRF7) mRNA, thereby inhibiting the DNA-sensing pathway. Loss of UL41 potently enhanced the IFN-β response to DEV and impaired viral replication in ducks. These findings provide insights into the host-virus interaction during DEV infection and help develop new live attenuated vaccines against DEV.
Topics: Animals; DNA, Viral; Ducks; Enteritis; Immunity, Innate; Interferon Regulatory Factor-7; Nucleotidyltransferases; Signal Transduction; Viral Proteins; Immune Evasion; Alphaherpesvirinae
PubMed: 36448809
DOI: 10.1128/jvi.01578-22 -
Microbiology Spectrum Dec 2022The cytosolic DNA sensing pathway mediates innate immune defense against infection by many DNA viruses; however, viruses have evolved multiple strategies to evade the...
The cytosolic DNA sensing pathway mediates innate immune defense against infection by many DNA viruses; however, viruses have evolved multiple strategies to evade the host immune response. Duck enteritis virus (DEV) causes an acute and contagious disease with high mortality in waterfowl. The mechanisms employed by DEV to block the DNA sensing pathway are not well understood. Here, we sought to investigate the role of DEV US3, a serine/threonine protein kinase, in the inhibition of DNA sensing. We found that ectopic expression of DEV US3 significantly inhibited the production of IFN-β and expression of interferon-stimulated genes induced by interferon-stimulatory DNA and poly(dA-dT). US3 also inhibited viral DNA-triggered IFN-β activation and promoted DEV replication in duck embryo fibroblasts, while knockdown of US3 during DEV infection enhances the IFN-β response and suppresses viral replication. US3 inhibited the DNA-sensing signaling pathway by targeting interferon regulatory factor 7 (IRF7), and the kinase activity of US3 was indispensable for its inhibitory function. Furthermore, we found that US3 interacts with the activation domain of IRF7, phosphorylating IRF7, blocking its dimerization and nuclear translocation, and finally leading to the inhibition of IFN-β production. These findings expand our knowledge on DNA sensing in ducks and reveal a novel mechanism whereby DEV evades host antiviral immunity. Duck enteritis virus (DEV) is a duck alphaherpesvirus that causes an acute and contagious disease with high mortality, resulting in substantial economic losses in the commercial waterfowl industry. The evasion of DNA-sensing pathway-mediated antiviral innate immunity is essential for the persistent infection and replication for many DNA viruses. However, the strategies used by DEV to block the DNA-sensing pathway are not well understood. In this study, DEV US3 protein kinase was demonstrated to inhibit the DNA-sensing signaling via binding to the activation domain of interferon regulatory factor 7 (IRF7), which induced the hyperphosphorylation of IRF7 and abolished IRF7 dimerization and nuclear translocation. Our findings provide insights into how duck herpesviral kinase counteracts host antiviral innate immunity to ensure viral replication and spread.
Topics: Animals; Antiviral Agents; DNA; Ducks; Enteritis; Immunity, Innate; Interferon Regulatory Factor-7; Interferon-beta; Interferons; Protein Kinases; Signal Transduction; Viral Proteins; Alphaherpesvirinae
PubMed: 36287016
DOI: 10.1128/spectrum.02299-22 -
The Indian Journal of Medical Research Apr 2017Opportunistic virus infections are common in liver transplant (LT) recipients. There is a risk of developing infection with cytomegalovirus (CMV) and herpes-related...
BACKGROUND & OBJECTIVES
Opportunistic virus infections are common in liver transplant (LT) recipients. There is a risk of developing infection with cytomegalovirus (CMV) and herpes-related viruses such as herpes simplex virus-1 and 2 (HSV-1 & 2), Epstein-Barr virus (EBV) and Varicella Zoster virus (VZV), reactivation of infection and recurrent infection. This study was conducted to determine CMV seropositivity in donors and its influence on LT recipients and seropositivity of CMV, HSV-1 and 2, EB viral capsid antigen (EBVCA) and VZV in LT recipients and their reactivation.
METHODS
Pre-transplant data for IgG and IgM for CMV (and donor), HSV-1 and -2, EB viral capsid antigen (VCA) and VZV were available for 153 recipients. All recipients were on ganciclovir or valganciclovir prophylaxis for three months after LT. For reactivation rates, findings of post-transplant CMV quantitative reverse transcription polymerase chain reaction (CMV qRT-PCR) assay were associated with pre-transplant serological profile.
RESULTS
Of the 153 LT recipients, 131 were men (85.6%). The median age of LT was 46 yr (range 9 months-71 yr). Overall exposure to CMV was 71.8 per cent followed by EB VCA (61.4%) and VZV (49.6%). Susceptibility to both HSV-1 and -2 was high across all decades (P<0.001). Seropositivity of CMV in donor was 90.9 per cent (100 out of 110). Post-transplant CMV qRT- PCR was positive in 17 (26.6%; 3 in recipient negative) of 64 samples tested. qRT-PCR assay was positive in one out of four (25%) tested for HSV-1 and nine out of 19 (47.4%) tested for EBV. Two recipients tested for HSV-2 and one for VZV were negative. There were three deaths in recipients (D+ R+) who were also positive for CMV qRT PCR. There was one death due to HSV-1 pneumonia. One patient with EBV reactivation developed post-transplant lymphoproliferative disorder two years after transplant.
INTERPRETATION & CONCLUSIONS
Transplant recipient were at highest risk of acquiring HSV-1 and -2 more so for HSV-2. CMV exposure in transplant recipients and donors were very high and at greatest risk for recipient reactivation rate. Despite this, death related to CMV reactivation was low.
Topics: Adolescent; Adult; Aged; Antibodies, Viral; Child; Child, Preschool; Cytomegalovirus; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Humans; Infant; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Seroepidemiologic Studies; Tissue Donors; Young Adult
PubMed: 28862190
DOI: 10.4103/ijmr.IJMR_1024_14