Herpes simplex virus and varicella-zoster virus: why do these human alphaherpesviruses behave so differently from one another?

Mori, Isamu; Nishiyama, Yukihiro

doi:10.1002/rmv.478

Cited by 34 publications

(23 citation statements)

References 118 publications

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“…Infection of PBMC arguably is the decisive step in the pathogenesis of EHV-1 and related herpesviruses such as PRV, because it enables the virus to evade the immune system while spreading systemically (5,9,10,15,16,45,46). Interestingly, lower viral titers were seen over time for EHV-4-infected PBMC, while the titers of EHV-1-infected PBMC remained constant.…”

Section: Discussionmentioning

confidence: 99%

“…Besides EHV-1, other alphaherpesviruses, such as varicella zoster virus (VZV) and pseudorabies virus (PRV), have been shown to cause cell-associated viremia, which contributes to the widespread distribution of virus and infection of organs (9,10). EHV-1 can replicate in PBMC in a restricted fashion and apparently fails to establish a productive infection (11)(12)(13).…”

Section: Importancementioning

confidence: 99%

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Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: a Dynamic In Vitro Model

Spiesschaert

Goldenbogen

Taferner

et al. 2015

J Virol

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Infected peripheral blood mononuclear cells (PBMC) effectively transport equine herpesvirus type 1 (EHV-1), but not EHV-4, to endothelial cells (EC) lining the blood vessels of the pregnant uterus or central nervous system, a process that can result in abortion or myeloencephalopathy. We examined, using a dynamic in vitro model, the differences between EHV-1 and EHV-4 infection of PBMC and PBMC-EC interactions. In order to evaluate viral transfer between infected PBMC and EC, cocultivation assays were performed. Only EHV-1 was transferred from PBMC to EC, and viral glycoprotein B (gB) was shown to be mainly responsible for this form of cell-to-cell transfer. For addressing the more dynamic aspects of PBMC-EC interaction, infected PBMC were perfused through a flow channel containing EC in the presence of neutralizing antibodies. By simulating capillary blood flow and analyzing the behavior of infected PBMC through live fluorescence imaging and automated cell tracking, we observed that EHV-1 was able to maintain tethering and rolling of infected PBMC on EC more effectively than EHV-4. Deletion of US3 reduced the ability of infected PBMC to tether and roll compared to that of cells infected with parental virus, which resulted in a significant reduction in virus transfer from PBMC to EC. Taking the results together, we conclude that systemic spread and EC infection by EHV-1, but not EHV-4, is caused by its ability to infect and/or reprogram mononuclear cells with respect to their tethering and rolling behavior on EC and consequent virus transfer. IMPORTANCEEHV-1 is widespread throughout the world and causes substantial economic losses through outbreaks of respiratory disease, abortion, and myeloencephalopathy. Despite many years of research, no fully protective vaccines have been developed, and several aspects of viral pathogenesis still need to be uncovered. In the current study, we investigated the molecular mechanisms that facilitate the cell-associated viremia, which is arguably the most important aspect of EHV-1 pathogenesis. The newly discovered functions of gB and pUS3 add new facets to their previously reported roles. Due to the conserved nature of cell-associated viremia among numerous herpesviruses, these results are also very relevant for viruses such as varicella-zoster virus, pseudorabies virus, human cytomegalovirus, and others. In addition, the constructed mutant and recombinant viruses exhibit potent in vitro replication but have significant defects in certain stages of the disease course. These viruses therefore show much promise as candidates for future live vaccines. E quine herpesvirus type 1 (EHV-1) and EHV-4 are members of the Herpesviridae family and Alphaherpesvirinae subfamily (1, 2). After initial replication in the upper respiratory tract, EHV-1 infects immune cells and migrates past the epithelial basement membrane to the lymph nodes and bloodstream (1-4). As a result, EHV-1 is able to spread throughout the body, where it infects endothelial cells (EC), causing vascular lesions an...

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Section: Discussionmentioning

confidence: 99%

Section: Importancementioning

confidence: 99%

Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: a Dynamic In Vitro Model

Spiesschaert

Goldenbogen

Taferner

et al. 2015

J Virol

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“…The virus also impairs expression of intracellular adhesion molecule 1 on the surface of infected keratinocytes [133]. These phenomena likely serve as important mechanisms by which the virus evades recognition by circulating CTLs [21,220].…”

Section: Immune Evasionmentioning

confidence: 98%

“…VZV is an alpha herpesvirus, members of which are characterised by a relatively short reproductive cycle, rapid cell-cell spread and their ability to establish latent infections primarily in sensory ganglia [21]. Alpha herpesviruses are divided into the genera Simplexvirus and Varicellovirus [22].…”

Section: Introductionmentioning

confidence: 99%

Molecular studies of Varicella zoster virus

Quinlivan

Breuer²

2006

Rev. Med. Virol.

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VZV is a highly cell-associated member of the Herpesviridae family and one of the eight herpesviruses to infect humans. The virus is ubiquitous in most populations worldwide, primary infection with which causes varicella, more commonly known as chickenpox. Characteristic of members of the alphaherpesvirus sub-family, VZV is neurotropic and establishes latency in sensory neurones. Reactivation from latency, usually during periods of impaired cellular immunity, causes herpes zoster (shingles). Despite being one of the most genetically stable human herpesviruses, nucleotide alterations in the virus genome have been used to classify VZV strains from different geographical regions into distinct clades. Such studies have also provided evidence that, despite pre-existing immunity to VZV, subclinical reinfection and reactivation of reinfecting strains to cause zoster is also occurring. During both primary infection and reactivation, VZV infects several PBMC and skin cell lineages. Difficulties in studying the pathogenesis of VZV because of its high cell association and narrow host range have been overcome through the development of the VZV severe combined immunodeficient mouse model carrying human tissue implants. This model has provided a valuable tool for studying the importance of individual viral proteins during both the complex intracellular replication and assembly of new virions and for understanding the underlying mechanism of attenuation of the live varicella vaccine. In addition, a rat model has been developed and successfully used to uncover which viral proteins are important for both the establishment and maintenance of latent VZV infection.

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“…The virus is transmitted readily by air or contact and thus is an important virus epidemiologically. Following primary infection which occurs usually in early childhood, the virus remains latent in the sensory ganglions throughout life [Mori and Nishiyama, 2005;Steiner et al, 2007]. VZV is an enveloped virus with a double-stranded linear DNA genome of approximately 125,000 bp.…”

Section: Introductionmentioning

confidence: 99%

Determination of the geographical origin of unidentified cadavers based on geographical differences in genotype of varicella–zoster virus

Inoue

Motani-Saitoh

Sakurada

et al. 2010

Journal of Medical Virology

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A new method was developed for determining the geographical origin of unidentified cadavers by examining the genome of varicella-zoster virus (VZV), which resides latently throughout life in most individuals and the genotypes which show distinct geographical distribution. VZV DNA samples extracted from the trigeminal ganglia of 62 cadavers (59 from Japan, and 1 each from the United Kingdom, Mongolia, and Pakistan) submitted for medico-legal autopsy were examined. Sequencing was performed on a 358-bp region in the open reading frame (ORF) 22 containing four single nucleotide polymorphisms (SNPs) and a 419-bp region in ORF 62 containing 2 SNPs in the VZV genome. Using these SNP markers, the VZV genome was classified into the nine genotypes described previously. Phylogenetic tree analysis was also undertaken for the sequenced regions and for the 22 existing VZV strains described previously. In addition, 21 samples were subcloned for detection of co-infection. The VZV genome was classified successfully into nine genotypes using four SNPs in ORF 22 and two SNPs in ORF 62 as markers. Among Japanese cadavers, 57 carried genotype J, 1 carried genotype M1, and 1 carried genotype M2. The British and the Mongolian cadavers carried genotype E1 and the Pakistani cadaver carried M1. Phylogenetic tree analysis showed that VZV strains can be classified into different genotypes with high bootstrap values. None of the subcloned samples showed evidence of co-infection. These results suggest that valuable additional information for determining the geographical origin of unidentified cadavers can be provided by examining the VZV genome.

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Herpes simplex virus and varicella-zoster virus: why do these human alphaherpesviruses behave so differently from one another?

Cited by 34 publications

References 118 publications

Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: a Dynamic In Vitro Model

Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: a Dynamic In Vitro Model

Molecular studies of Varicella zoster virus

Determination of the geographical origin of unidentified cadavers based on geographical differences in genotype of varicella–zoster virus

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