Pangaea and the Out-of-Africa Model of Varicella-Zoster Virus Evolution and Phylogeography

Grose, Charles

doi:10.1128/jvi.00357-12

Cited by 65 publications

(59 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the coevolution of humans and HSV-1, spatial segregation of ancestral host populations is likely to have generated some geographic isolation of viral lineages. Similar impacts of geographic separation on the results of viral genome clustering have been observed for VZV (12,15,155,156). The current study, in combination with prior work, indicates extensive recombination between HSV-1 genomes (Fig.…”

Section: Aa Alignment Of the Divergent Hsv-1 Us11 Proteinsupporting

confidence: 73%

See 1 more Smart Citation

Evolution and Diversity in Human Herpes Simplex Virus Genomes

Szpara

Gatherer

Ochoa

et al. 2014

J Virol

199

280

View full text Add to dashboard Cite

gHerpes simplex virus 1 (HSV-1) causes a chronic, lifelong infection in >60% of adults. Multiple recent vaccine trials have failed, with viral diversity likely contributing to these failures. To understand HSV-1 diversity better, we comprehensively compared 20 newly sequenced viral genomes from China, Japan, Kenya, and South Korea with six previously sequenced genomes from the United States, Europe, and Japan. In this diverse collection of passaged strains, we found that one-fifth of the newly sequenced members share a gene deletion and one-third exhibit homopolymeric frameshift mutations (HFMs). Individual strains exhibit genotypic and potential phenotypic variation via HFMs, deletions, short sequence repeats, and single-nucleotide polymorphisms, although the protein sequence identity between strains exceeds 90% on average. In the first genome-scale analysis of positive selection in HSV-1, we found signs of selection in specific proteins and residues, including the fusion protein glycoprotein H. We also confirmed previous results suggesting that recombination has occurred with high frequency throughout the HSV-1 genome. Despite this, the HSV-1 strains analyzed clustered by geographic origin during whole-genome distance analysis. These data shed light on likely routes of HSV-1 adaptation to changing environments and will aid in the selection of vaccine antigens that are invariant worldwide. Herpes simplex virus 1 (HSV-1; species Human herpesvirus 1, genus Simplexvirus, subfamily Alphaherpesvirinae, family Herpesviridae, order Herpesvirales) is among the most successful human pathogens in terms of its global distribution, longevity in the host, and mild symptoms among the great majority of those exposed (1-4). HSV-1 is a large, enveloped DNA virus that infects lytically at epithelial surfaces and establishes a lifelong, latent infection in sensory neurons. HSV-1 infection produces a wide range of symptoms, ranging from few or none in many seropositive individuals to periodic lesions on epithelial surfaces in a significant proportion of people and to lethal encephalitis as an extreme manifestation in a few. There is no vaccine at present (5, 6). Studies in animal models have characterized the ways in which genetic variation between viral strains can influence the symptoms of pathology, including lesion severity and rates of reactivation from latency. The most recent phase III vaccine trial for HSV failed to provide protection from infection (7, 8), and one contributing factor to this failure may well be variation among HSV isolates found in the field.Based on early restriction fragment length polymorphism (RFLP) analyses, HSV-1 has been described as more diverse than HSV-2 (9-11). In contrast to both HSV-1 and HSV-2, the related human alphaherpesvirus, varicella-zoster virus (VZV), has relatively low interstrain diversity (12-15). Decades of research comparing RFLP bands, polypeptide size, and PCR-based sequence analysis have revealed that HSV-1 strains vary between individuals, over sequential isolates from the s...

show abstract

Section: Aa Alignment Of the Divergent Hsv-1 Us11 Proteinsupporting

confidence: 73%

“…9), at a level that far exceeds that observed for VZV (13,15,156). While dating of VZV evolution has been proposed based on similar data, we find that the prevalence of recombination in HSV-1 makes it unwise to add a time scale to internal nodes or to interpret these clusters as clades (13,155,157).…”

Section: Aa Alignment Of the Divergent Hsv-1 Us11 Proteinmentioning

confidence: 41%

Evolution and Diversity in Human Herpes Simplex Virus Genomes

Szpara

Gatherer

Ochoa

et al. 2014

J Virol

199

280

View full text Add to dashboard Cite

show abstract

“…In addition, many such as VZV lack an ortholog of US11 (31). VZV with the smallest herpesvirus genome, therefore, has discarded US11 (or never acquired it) and never captured the ICP34.5/ GADD34-homolog gene during its evolution (32).…”

Section: Discussionmentioning

confidence: 99%

Autophagic flux without a block differentiates varicella-zoster virus infection from herpes simplex virus infection

Buckingham

Carpenter

Jackson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Autophagy is a process by which misfolded and damaged proteins are sequestered into autophagosomes, before degradation in and recycling from lysosomes. We have extensively studied the role of autophagy in varicella-zoster virus (VZV) infection, and have observed that vesicular cells are filled with >100 autophagosomes that are easily detectable after immunolabeling for the LC3 protein. To confirm our hypothesis that increased autophagosome formation was not secondary to a block, we examined all conditions of VZV infection as well as carrying out two assessments of autophagic flux. We first investigated autophagy in human skin xenografts in the severe combined immunodeficiency (SCID) mouse model of VZV pathogenesis, and observed that autophagosomes were abundant in infected human skin tissues. We next investigated autophagy following infection with sonically prepared cell-free virus in cultured cells. Under these conditions, autophagy was detected in a majority of infected cells, but was much less than that seen after an infected-cell inoculum. In other words, inoculation with lower-titered cell-free virus did not reflect the level of stress to the VZV-infected cell that was seen after inoculation of human skin in the SCID mouse model or monolayers with higher-titered infected cells. Finally, we investigated VZVinduced autophagic flux by two different methods (radiolabeling proteins and a dual-colored LC3 plasmid); both showed no evidence of a block in autophagy. Overall, therefore, autophagy within a VZV-infected cell was remarkably different from autophagy within an HSV-infected cell, whose genome contains two modifiers of autophagy, ICP34.5 and US11, not present in VZV.V ZV induces macroautophagy (hereafter referred to as autophagy) in skin cells within the typical exanthem associated with either primary VZV infection (varicella or chickenpox) or VZV reactivation (herpes zoster or shingles). During prior studies, the extent of autophagy was gauged by enumeration of autophagosomes by both 2D and 3D microscopy (1, 2). The usual number of autophagosomes seen by 3D animation was 100 per infected cell, but sometimes approached 200 per cell. In contrast, a typical nonstressed cell usually has fewer than 4 autophagosomes (3, 4). When monolayers were inoculated with VZV-infected cells, the traditional method for VZV infection, autophagy was again easily seen after enumeration of autophagosomes and immunoblotting for the LC3-phosphatidylethanolamine conjugate (LC3-II). Again these results suggested that autophagic flux was present during VZV infection in cultured cells.As part of a more extensive assessment of autophagy after VZV-induced cellular stress, we have now investigated autophagy in infected human skin xenografts from the SCID mouse model of VZV infection. This model is the most accurate representation of the skin manifestation of varicella in the human host (5, 6). Finally, we addressed an important point about the nature of VZV-induced autophagy. Because the number of autophagosomes seen in the human vesicle...

show abstract

“…Many herpesviruses, such as herpes simplex virus, encode inhibitors of autophagy, including ICP34.5 and US11 . By contrast, VZV -the human herpesvirus with the smallest genome -encodes no such inhibitors [196][197][198] .…”

Section: Autophagy and Herpesvirusesmentioning

confidence: 99%