Scientists probing the details of viral infection have discovered an intriguing surprise: in mice, herpes viruses hijack their host cells' tools for fixing DNA damage and use those tools to enhance their own reproduction.
The DNA damage response normally fixes DNA errors caused by radiation or other environmental factors, or mistakes accidentally introduced when cells copy their genetic material prior to dividing.
In the murine (or mouse-infecting) herpes virus they studied, researchers at Washington University School of Medicine in St. Louis identified a protein that can trick the mouse cell into turning on the DNA damage response. They also showed that Epstein-Barr virus, a human herpes virus, has a similar protein. Scientists found that blocking murine herpes virus from activating the DNA damage response caused viral replication rates to plummet.
"We don't want to treat viral infection by blocking DNA damage response systemically because this process is used constantly throughout the body and is very important to preventing cancer," says lead author Vera Tarakanova, Ph.D., a postdoctoral fellow. "However, by targeting the viral protein responsible for activating the DNA damage response, we may be able to block viral replication. In addition, determining how the DNA repair response helps viral replication may enable us to develop novel strategies to treat infection."
The paper appears online this week in Cell Host & Microbe. Scientists have known for some time that viral infection of cells activates the DNA damage response. But researchers had assumed that this activation occurred because repair mechanisms were mistaking replicating viral DNA for damaged or dysfunctional cellular DNA.
"Viruses sometimes structure their own DNA differently than cellular DNA," Tarakanova notes. "Many of us thought that such differences might be triggering the DNA damage response." Working in the laboratory of Herbert W. "Skip" Virgin, M.D., Ph.D., Edward Mallinckrodt Professor and head of the Department of Pathology and Immunology, Tarakanova found that murine herpes virus, rather than the host cell, was triggering the DNA damage response. She showed that introducing just one viral protein into cells led to activation of two cellular proteins involved in the damage response, ATM and H2AX.
The viral protein that triggered this inappropriate activation, orf36, is a kinase, a type of protein that chemically modifies other molecules to activate different processes or transmit signals. Genetic comparisons with several human herpes viruses revealed kinases similar to orf36 in the human viruses. Scientists then took a similar kinase from human Epstein-Barr virus and showed that introducing it into cells also activated the DNA damage response.
When the research team genetically disabled orf36 in the murine herpes virus and infected mouse cells with it, the virus no longer activated the DNA damage response. The virus's ability to replicate also dramatically decreased.
Kinases are versatile proteins that sometimes play multiple roles. To ensure that enhanced viral replication wasn't linked to orf36's interactions with other molecules, researchers turned to mice lacking the genes for ATM and H2AX, the damage response proteins activated by infection. When they infected cells from these mice with murine herpes virus, its ability to reproduce was again curtailed. How DNA damage response benefits viral replication is still a mystery and a topic of continuing investigation in the Virgin lab.
"The discovery that induction of the cells' DNA damage response is an intentional viral strategy, rather than a passive cellular response to viral invasion, means that we should look into whether other DNA viruses use a similar approach to enhance their growth," says Virgin.
Living with STD, but not alone!
Sunday, June 17, 2007
Tuesday, June 12, 2007
Effects of Herpesvirus on Pregnancy
The severity of symptoms depends on where and howthe virus gains entry into the body. Except in veryrare instances and in special circumstances, thedisease is not life threatening, although it can bevery debilitating and cause great emotionaldistress.Effects of Herpesvirus on Pregnancy Pregnantwomen who are infected with either HSV-2 or HSV-1genital herpes have a higher risk for miscarriage,premature labor, retarded fetal growth, ortransmission of the HSV infection to the infantwhile in the uterus or at the time of delivery. Onestudy also suggested a link between HSV-2 infectionin mothers and the subsequent development ofschizophrenia and other forms of psychoses in theiradult offspring, although further study is needed.Recurrence in women previously infected with HSV isalso common during pregnancy. It should be noted,however, that about one million pregnancies occureach year in women who have been infected withHSV-2, but complications occur in only .01% to .04%of all infected pregnant women.
Living with STD, but not alone!
Living with STD, but not alone!
Monday, June 11, 2007
Treatment of molluscum contagiosum and herpes simplex virus cutaneous infections.
Molluscum contagiosum (MC) is a human viral infection contracted by skin-to-skin inoculation, autoinoculation, and fomite inoculation. There are a variety of treatments for MC, including watchful waiting, curettage, cantharidin, cryotherapy, and topical imiquimod. Herpes simplex virus (HSV) infections also have been treated with imiquimod. This article discusses the treatment of MC and HSV infections and reviews the literature.
Living with STD, but not alone!
Living with STD, but not alone!
Study Published in Sexually Transmitted Diseases Journal Shows Herpes Is Common in Suburban Populations
According to a recent study of 36 primary care physician (PCP) offices in relatively affluent suburban areas of six U.S. cities, one in four people (25.5 percent) tested positive for the virus that causes genital herpes, despite the fact that only four percent of all those tested reported a history of the condition. As the study shows, genital herpes infection rates were high even among suburban, educated and mid to high income populations. The results of this study were published in this month's issue of Sexually Transmitted Diseases.
"Genital herpes continues to spread because very few people with the virus know they have it. The prevalence statistics are important for both patients and doctors because they show that people of all backgrounds are at high risk for contracting genital herpes. This is especially important because people can be contagious even when they do not have symptoms of infection," said Peter Leone, lead author of the study and an associate professor of medicine at the University of North Carolina at Chapel Hill. "The study should encourage everyone to practice safer sex, get tested, and if they are infected learn how to manage the disease."
ABOUT THE STUDY
The study took place at six randomly selected PCP offices in relatively affluent areas in each of six U.S. cities (Atlanta, Baltimore, Boston, Chicago, Dallas, Denver). At each office, approximately 150 people age 18-59 were randomly chosen to participate. All blood samples were sent to a central laboratory. A positive test result indicated they were infected with HSV-2, the virus that causes genital herpes (GH). All samples were analyzed using the Focus Technologies HerpeSelect® 2 ELISA IgG test designed specifically to detect HSV-2 antibodies in the blood.
In total, 5,732 people were screened; of 5,452 people who provided an analyzable blood sample, 5,433 completed a questionnaire. The final sample was 75 percent white, 14 percent African American, and 4 percent Hispanic. Eighty percent were employed full- or part-time, 74 percent had some college or higher education, 45 percent had a household income of $60,000 or higher, and 68 percent were married/living with their partner.
The overall weighted HSV-2 seroprevalence was 25.5 percent -- that means 1 in 4 people tested positive for the virus that causes genital herpes. The seroprevalence ranged from 13.4 percent in the 18-29-year age group, to 25.2 percent (30-39 years), to 31.2 percent (40-49 years) and 28.0 percent (50-59 years). Seroprevalence among women (28.3 percent) was greater than that among men (22.0 percent), and was consistently higher across all age groups. Of the 1,387 people that tested positive for genital herpes, only 12 percent knew they were infected.
The study showed that employment status, marital status and income did not reduce the chances of having genital herpes. Those who were employed full-time had a prevalence of 26 percent, married individuals had a prevalence of 24 percent, those living with their partners had a prevalence of 26 percent, and those with household incomes of $60,000-$80,000 had a prevalence of 24 percent while those with incomes over $100,000 had a prevalence of 21 percent. Those with some college had a prevalence of 28 percent and college graduates had a prevalence of 21 percent.
The study was sponsored by GlaxoSmithKline, one of the world's leading research-based pharmaceutical and health care companies.
About Genital Herpes
In 1991, an estimated 1 in 5, or 45 million, Americans were infected with the virus that causes genital herpes. Experts estimate that up to 60 million Americans have the virus that causes genital herpes and the CDC estimates that approximately 1 million people are infected each year. However, as many as nine out of ten of those infected are unaware they have genital herpes and may only have experienced a mild initial outbreak without recognizing recurring symptoms of the disease. Symptoms of genital herpes may include painful or itchy clusters of blisters, bumps and rashes in the genital area, or on the thighs or buttocks. Many people confuse genital herpes symptoms with other conditions such as urinary tract infections (UTIs), ingrown hair, jock itch, zipper burn, allergic reactions, vaginal infections, a cut or a scratch, or irritation from sexual intercourse or tight jeans.
Though the disease is most contagious during an outbreak, it can also be contagious between outbreaks when no signs and symptoms are present. In fact, in clinical studies, the majority of people got genital herpes from a partner who knew they had genital herpes but reported no signs or symptoms at the time of recent sexual activity.
Living with STD, but not alone!
"Genital herpes continues to spread because very few people with the virus know they have it. The prevalence statistics are important for both patients and doctors because they show that people of all backgrounds are at high risk for contracting genital herpes. This is especially important because people can be contagious even when they do not have symptoms of infection," said Peter Leone, lead author of the study and an associate professor of medicine at the University of North Carolina at Chapel Hill. "The study should encourage everyone to practice safer sex, get tested, and if they are infected learn how to manage the disease."
ABOUT THE STUDY
The study took place at six randomly selected PCP offices in relatively affluent areas in each of six U.S. cities (Atlanta, Baltimore, Boston, Chicago, Dallas, Denver). At each office, approximately 150 people age 18-59 were randomly chosen to participate. All blood samples were sent to a central laboratory. A positive test result indicated they were infected with HSV-2, the virus that causes genital herpes (GH). All samples were analyzed using the Focus Technologies HerpeSelect® 2 ELISA IgG test designed specifically to detect HSV-2 antibodies in the blood.
In total, 5,732 people were screened; of 5,452 people who provided an analyzable blood sample, 5,433 completed a questionnaire. The final sample was 75 percent white, 14 percent African American, and 4 percent Hispanic. Eighty percent were employed full- or part-time, 74 percent had some college or higher education, 45 percent had a household income of $60,000 or higher, and 68 percent were married/living with their partner.
The overall weighted HSV-2 seroprevalence was 25.5 percent -- that means 1 in 4 people tested positive for the virus that causes genital herpes. The seroprevalence ranged from 13.4 percent in the 18-29-year age group, to 25.2 percent (30-39 years), to 31.2 percent (40-49 years) and 28.0 percent (50-59 years). Seroprevalence among women (28.3 percent) was greater than that among men (22.0 percent), and was consistently higher across all age groups. Of the 1,387 people that tested positive for genital herpes, only 12 percent knew they were infected.
The study showed that employment status, marital status and income did not reduce the chances of having genital herpes. Those who were employed full-time had a prevalence of 26 percent, married individuals had a prevalence of 24 percent, those living with their partners had a prevalence of 26 percent, and those with household incomes of $60,000-$80,000 had a prevalence of 24 percent while those with incomes over $100,000 had a prevalence of 21 percent. Those with some college had a prevalence of 28 percent and college graduates had a prevalence of 21 percent.
The study was sponsored by GlaxoSmithKline, one of the world's leading research-based pharmaceutical and health care companies.
About Genital Herpes
In 1991, an estimated 1 in 5, or 45 million, Americans were infected with the virus that causes genital herpes. Experts estimate that up to 60 million Americans have the virus that causes genital herpes and the CDC estimates that approximately 1 million people are infected each year. However, as many as nine out of ten of those infected are unaware they have genital herpes and may only have experienced a mild initial outbreak without recognizing recurring symptoms of the disease. Symptoms of genital herpes may include painful or itchy clusters of blisters, bumps and rashes in the genital area, or on the thighs or buttocks. Many people confuse genital herpes symptoms with other conditions such as urinary tract infections (UTIs), ingrown hair, jock itch, zipper burn, allergic reactions, vaginal infections, a cut or a scratch, or irritation from sexual intercourse or tight jeans.
Though the disease is most contagious during an outbreak, it can also be contagious between outbreaks when no signs and symptoms are present. In fact, in clinical studies, the majority of people got genital herpes from a partner who knew they had genital herpes but reported no signs or symptoms at the time of recent sexual activity.
Living with STD, but not alone!
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