Dataset Information

Large, Stable, Contemporary Interspecies Recombination Events in Circulating Human Herpes Simplex Viruses.

ABSTRACT:

Background

The ubiquitous human pathogens, herpes simplex virus (HSV)-1 and HSV-2, are distinct viral species that diverged approximately 6 million years ago. At least 4 small, ancient HSV-1 × HSV-2 interspecies recombination events have affected the HSV-2 genome, with recombinants and nonrecombinants at each locus circulating today. However, it is unknown whether interspecies recombination can affect other loci and whether new recombinants continue to be generated.

Methods

Using 255 newly sequenced and 230 existing HSV genome sequences, we comprehensively assessed interspecies recombination in HSV.

Results

Our findings show that the sizes and locations of interspecies recombination events in HSV-2 are significantly more variable than previously appreciated and that they can impact species-specific T-cell recognition of HSV.

Conclusions

We describe 2 large (>5 kb) recombination events, one of which arose in its current host, demonstrating that interspecies recombination continues to occur today. These results raise concerns about the use of live-attenuated HSV-2 vaccines in high HSV-1 prevalence areas.

SUBMITTER: Casto AM

PROVIDER: S-EPMC7325804 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Large, Stable, Contemporary Interspecies Recombination Events in Circulating Human Herpes Simplex Viruses.

Casto Amanda M AM Roychoudhury Pavitra P Xie Hong H Selke Stacy S Perchetti Garrett A GA Wofford Haley H Huang Meei-Li ML Verjans Georges M G M GMGM Gottlieb Geoffrey S GS Wald Anna A Jerome Keith R KR Koelle David M DM Johnston Christine C Greninger Alexander L AL

The Journal of infectious diseases 20200301 8

<h4>Background</h4>The ubiquitous human pathogens, herpes simplex virus (HSV)-1 and HSV-2, are distinct viral species that diverged approximately 6 million years ago. At least 4 small, ancient HSV-1 × HSV-2 interspecies recombination events have affected the HSV-2 genome, with recombinants and nonrecombinants at each locus circulating today. However, it is unknown whether interspecies recombination can affect other loci and whether new recombinants continue to be generated.<h4>Methods</h4>Using ...[more]

PMID: 31016321

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Project description:Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed "latency", which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish. Currently, there are no effective FDA-approved vaccines for either prophylactic or therapeutic treatment of human herpes simplex infections, while several recent clinical trials have failed to achieve their endpoint goals. Historically, live-attenuated vaccines have successfully combated viral diseases, including polio, influenza, measles, and smallpox. Vaccines aimed to protect against the devastation of smallpox led to the most significant achievement in medical history: the eradication of human disease by vaccination. Recently, novel approaches toward developing safe and effective live-attenuated vaccines have demonstrated high efficacy in various preclinical models of herpetic disease. This next generation of live-attenuated vaccines has been tailored to minimize vaccine-associated side effects and promote effective and long-lasting immune responses. The ultimate goal is to prevent or reduce primary infections (prophylactic vaccines) or reduce the frequency and severity of disease associated with reactivation events (therapeutic vaccines). These vaccines' "rational" design is based on our current understanding of the immunopathogenesis of herpesviral infections that guide the development of vaccines that generate robust and protective immune responses. This review covers recent advances in the development of herpes simplex vaccines and the current state of ongoing clinical trials in pursuit of an effective vaccine against herpes simplex virus infections and associated diseases.

Dataset Information

Large, Stable, Contemporary Interspecies Recombination Events in Circulating Human Herpes Simplex Viruses.

Background

Methods

Results

Conclusions

Publications

Large, Stable, Contemporary Interspecies Recombination Events in Circulating Human Herpes Simplex Viruses.

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