Genome Sequence of Herpes Simplex Virus 1 Strain KOS

Macdonald, Stuart J.; Mostafa, Heba H.; Morrison, Lynda A.; Davido, David J.

doi:10.1128/jvi.00646-12

Cited by 72 publications

(75 citation statements)

References 13 publications

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“…For MS analyses, cells were infected at a multiplicity of infection (moi) of 3.0 TCID 50 /cell. Herpes simplex virus-1 (HSV, strain KOS 1.1) (14) and adenovirus type 5 (Ad5) (15) were also used in this study.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Proteomic Discovery of Dynamic Epigenome Changes that Control Human Cytomegalovirus (HCMV) Infection

O’Connor

DiMaggio

Shenk

et al. 2014

Molecular & Cellular Proteomics

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This work represents the first comprehensive quantitative analysis of global histone post-translational modifications (PTMs) from a virus infection, namely human cytomegalovirus (HCMV) infection. We used a nanoLC-MS/MS platform to identify and quantify the dynamic histone H3 and H4 PTMs expressed during HCMV replication in primary fibroblasts. Specifically, we examined the changes in histone PTMs over a 96 h time course to sample the immediate early (IE), early (E), and late (L) stages of viral infection. Several changes in histone H3 and H4 PTMs were observed, including a marked increase in H3K79me2 and H3K27me3K36me2, and a decrease in H4K16ac, highlighting likely epigenetic strategies of transcriptional activation and silencing during HCMV lytic infection. Heavy methyl-SILAC (hm-SILAC) was used to further confirm the histone methylation flux (especially for H3K79) during HCMV infection. We evaluated DOT1L (the H3K79 methyltransferase) mRNA levels in mock and HCMV-infected cells over a 96 h time course, and observed a significant increase in this methyltransferase as early as 24 hpi showing that viral infection up-regulates DOT1L expression, which drives H3K79me2. We then used shRNA to create a DOT1L knockdown cell population, and found that HCMV infection of the knockdown cells resulted in a 10-fold growth defect when compared with infected control cells not subjected to knockdown. This work documents multiple histone PTMs that occur in response to HCMV infection of fibroblasts, and provides a framework for evaluation of the role of epigenetic modifications in the virus-host interaction. Molecular & Cellular Proteomics

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Section: Methodsmentioning

confidence: 99%

Quantitative Proteomic Discovery of Dynamic Epigenome Changes that Control Human Cytomegalovirus (HCMV) Infection

O’Connor

DiMaggio

Shenk

et al. 2014

Molecular & Cellular Proteomics

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“…We did not have access to sequence read data for strains HF10, KOS, and McKrae, and we used these genome sequences as recorded in GenBank. Both records for KOS are listed in Table 1; we used the record published under accession number JQ673480 for the genomewide alignment (48). For McKrae, we used the genome sequence from the record published under accession number JQ730035 (49).…”

Section: Viruses and Sequencingmentioning

confidence: 99%

“…Six previously sequenced HSV-1 strains were included in the analysis, with data derived from each strain's GenBank record and associated publication(s). The publications describing these sequenced genomes are as follows, and the accession numbers for each sequence are listed in Table 1: 17 (43)(44)(45)(46), HF10 (47), F (29), H129 (29), KOS (48), and McKrae (49,50). Since the geographic origin of HSV-1 strains is considered in our analyses, the publications describing the first isolation and geographic origin of each strain are as follows: 17 (51), F (52), H129 (53), KOS (54), and McKrae (55).…”

Section: Viruses and Sequencingmentioning

confidence: 99%

Evolution and Diversity in Human Herpes Simplex Virus Genomes

Szpara

Gatherer

Ochoa

et al. 2014

J Virol

199

280

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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...

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“…In particular, the HSV-1 ICP4 protein is a major factor responsible for inducing corneal lymphangiogenesis by driving vascular endothelial growth factor (VEGF) expression in infected corneal epithelial cells (72). As discussed previously, the HSV-1 KOS strain does not induce the same extent of corneal pathology as other strains often used for laboratory research (38)(39)(40). This was underscored by the small degree of corneal neovascularization observed in WT mice infected with HSV-1 KOS-GFP (Fig.…”

Section: Discussionmentioning

confidence: 95%

“…However, HSV-1 McKrae exhibits greater neuroinvasiveness and pathogenicity than HSV-1 KOS in vivo (38)(39)(40). Nonetheless, all CD118 Ϫ/Ϫ mice infected with HSV-1 KOS-GFP (1 ϫ 10 5 PFU) by either the ocular or intranasal route expired by day 9 p.i.…”

mentioning

confidence: 99%

Impact of Type I Interferon on the Safety and Immunogenicity of an Experimental Live-Attenuated Herpes Simplex Virus 1 Vaccine in Mice

Royer

Carr

Chucair-Elliott

et al. 2017

J Virol

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Viral fitness dictates virulence and capacity to evade host immune defenses. Understanding the biological underpinnings of such features is essential for rational vaccine development. We have previously shown that the live-attenuated herpes simplex virus 1 (HSV-1) mutant lacking the nuclear localization signal (NLS) on the ICP0 gene (0ΔNLS) is sensitive to inhibition by interferon beta (IFN-␤) in vitro and functions as a highly efficacious experimental vaccine. Here, we characterize the host immune response and in vivo pathogenesis of HSV-1 0ΔNLS relative to its fully virulent parental strain in C57BL/6 mice. Additionally, we explore the role of type 1 interferon (IFN-␣/␤) signaling on virulence and immunogenicity of HSV-1 0ΔNLS and uncover a probable sex bias in the induction of IFN-␣/␤ in the cornea during HSV-1 infection. Our data show that HSV-1 0ΔNLS lacks neurovirulence even in highly immunocompromised mice lacking the IFN-␣/␤ receptor. These studies support the translational viability of the HSV-1 0ΔNLS vaccine strain by demonstrating that, while it is comparable to a virulent parental strain in terms of immunogenicity, HSV-1 0ΔNLS does not induce significant tissue pathology.IMPORTANCE HSV-1 is a common human pathogen associated with a variety of clinical presentations ranging in severity from periodic "cold sores" to lethal encephalitis. Despite the consistent failures of HSV subunit vaccines in clinical trials spanning the past 28 years, opposition to live-attenuated HSV vaccines predicated on unfounded safety concerns currently limits their widespread acceptance. Here, we demonstrate that a live-attenuated HSV-1 vaccine has great translational potential.KEYWORDS HSV-1, T cells, antibody, cornea, mouse, neovascularization S trategies for vaccine development have transitioned largely from empirical to so-called "next-generation" or rational approaches during the past 2 decades, a shift largely driven by technological advances and a better understanding of how innate immunity influences the generation of adaptive protection (1, 2). Despite these breakthroughs, the average person still acquires multiple herpesvirus infections during childhood (3). A licensed vaccine, however, exists only for varicella-zoster virus (VZV) (4). The live-attenuated Oka vaccine for VZV is generally well tolerated and has significantly reduced the incidence of VZV infection, morbidity, and mortality in the United States (5, 6). Furthermore, epidemiologic studies indicate that acquisition of herpes simplex virus 1 (HSV-1) has shifted toward early to late adolescence in recent decades within the United States, potentially creating an opportunity to introduce an effective prophylactic HSV-1 vaccine into the childhood vaccine regimen (7). HSV vaccines have been tested in multiple clinical trials, but these studies have focused on protein subunit vaccines

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Genome Sequence of Herpes Simplex Virus 1 Strain KOS

Cited by 72 publications

References 13 publications

Quantitative Proteomic Discovery of Dynamic Epigenome Changes that Control Human Cytomegalovirus (HCMV) Infection

Quantitative Proteomic Discovery of Dynamic Epigenome Changes that Control Human Cytomegalovirus (HCMV) Infection

Evolution and Diversity in Human Herpes Simplex Virus Genomes

Impact of Type I Interferon on the Safety and Immunogenicity of an Experimental Live-Attenuated Herpes Simplex Virus 1 Vaccine in Mice

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