New Study Links Genetics to Herpes Susceptibility

A new study published in the February 1 issue of The Journal of Infectious Diseases, shows new evidentiary support that a link exists between genetics and susceptibility to the herpes simplex virus. The study, now available online, has implications for the discovery of specific genes that could influence the frequency of herpes outbreaks in patients.

Herpes simplex virus (HSV) infection is very common in the United States, with about 70 percent of adults infected with HSV-1, which is linked primarily to oral herpes, and an estimated 17 percent infected with HSV type 2 (HSV-2), which is linked primarily to genital herpes. Herpes simplex is a persistent virus that causes not only a primary reaction, but also outbreaks throughout an infected patients lifetime.   There is currently no cure for herpes simplex, but treatments exist to alleviate its various symptoms and to help decrease contagious periods. 

Reactivations of HSV-1 cause herpes simplex labialis (HSL), the most common recurring viral infection in humans, commonly known as cold sores or fever blisters. Between 20 and 40 percent of the population will experience these outbreaks in their lifetime, although the frequency and severity of these outbreaks is variable. 

This study is the first to use linkage analysis in a whole genome study of HSV in humans.  It shows that a specific region on human chromosome 21 contains six genes that are candidates for influencing the frequency of HSL outbreaks.

The study, conducted by John D. Kriesel, MD, Maurine Hobbs, PhD, and colleagues at the University of Utah School of Medicine, analyzed 327 individuals infected with HSV-1 from the Utah Genetic Reference Project.  Genetic data across the entire human genome was used for linkage analysis, which looks for genes linked on a chromosome and therefore inherited together.  Subjects were grouped by the frequency of HSL symptoms and genetic analysis was done on those at the opposite ends of the spectrum in terms of frequency of outbreaks. 

Many genetic investigators start with the thought I think genes X, Y, and Z are important.  We didnt do that, Kriesel said. Our study held no preconceptions about which regions of the human genome might confer susceptibility to herpes. Therefore, the study was unbiased and it led to a place we never expected, chromosome 21. 

As a next step, Kriesel said he and his co-authors have already begun investigating the six candidate genes, hoping to discover which are directly related to HSL susceptibility.

We anticipate that one or more of the genes in this region could help guide future drug development, Kriesel said.  One of these genes, its RNA transcript, or its protein product might make an excellent drug target to reduce the frequency of HSV reactivation.  This would be especially valuable if our findings, currently limited to cold sores, can be extended to herpes keratitis or genital herpes. 

David M. Koelle, MD, and Tracy L. Bergemann, PhD, both of the University of Washington, echoed the need for such follow-up studies, saying future research would lead to discoveries for the general population of HSV-infected persons who are looking for answers concerning their chronic, and currently incurable, infections.

Source: Infectious Diseases Society of America (IDSA)