Herpes may disarm immune system.

Herpes may disarm immune system

Recurrent genital sores and fever blisters on the mouth provide two of the more painful reminders that infection with herpes simplex virus (HSV) persists for life. Although researchers know HSV's two strains can lie dormant in several tissues, the question remains: Why doesn't the immune system eliminate them?

New in vitro findings suggest an answer. Researchers at the University of Minnesota in Minneapolis report that prolonged contact with HSV-infected cells disarms key components of the immune system, preventing them from attacking the virus or several other infectious agents they would normally destroy. The laboratory work not only offers an explanation for HSV's persistence, but also suggests the virus may help other pathogens escape immune obliteration.

Dennis L. Confer, Harry S. Jacob and their colleagues began their study after noting a puzzling phenomenon among kidney transplant patients experimentally given a protective dose of the anti-HSV drug acyclovir. (Organ transplants carry a risk of transmitting the virus.) As expected, these patients showed a lower incidence of HSV infection than did transplant patients not receiving acyclovir. But the drug had another payoff: Treated patients also had lower rates of cytomegalovirus (CMV) infection, even though laboratory tests suggest that acyclovir cannot block CMV replication at the low doses used in the study.

The observation prompted Confer's group to investigate how the two HSV strains -- HSV-I, which causes oral herpes, and HSV-II, which causes genital herpes -- might promote other infections. They covered HSV-infected cells removed from human foreskin and blood vessel walls with a layer of one of two types of immune-system cells, natural killer (NK) cells or or interleukin-2-activated killer (LAK) cells. After eight hours of direct contact with the infected cells in culture plates, the immune cells lost their ability to attack the virus. Moreover, they could no longer destroy two

laboratory lines of human leukemia cells, the researchers say.

"Rather than a 'kiss of death,' contact with HSV-infected cells gives NK and LAK cells a 'kiss of paralysis,'" says Jacob. He suggests the finding may explain how acyclovir might reduce the success rate of other infectious agents. In the May PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol. 87, No. 9), the Minnesota researchers report that several of their tests strongly indicate the immune cells themselves were not infected. Instead, they propose that an HSV glycoprotein on the surface of the infected cells eventually disarms LAK and NK cells. The team found that when they chemically prevented HSV glycoproteins from forming, infected cells no longer inhibited immune-cell function. Other researchers have reported that an AIDS virus glycoprotein similarly disables NK cells.

Immunologist Ronald B. Herberman, who directs the University of Pittsburgh Cancer Institute, cautions that the laboratory work will remain inconclusive until researchers can establish a firm link between HSV and immunologic impairment in humans. Confer suggests looking for impaired LAK and NK cells in blood from HSV patients who harbor the virus in the cells lining their vessel walls.

HSV may promote cancerous changes independent of its effect on the immune system. For two decades, researchers have compiled strong evidence linking cervical cancer to both HSV-II and human papillomavirus, another sexually transmitted agent. Joseph A. DiPaolo of the National Cancer Institute told SCIENCE NEWS he and his colleagues recently found that a laboratory cell line of papilloma-infected genital epithelial cells changed into carcinoma cells when exposed to HSV-II. DiPaolo says the transformation, which his team will detail in a forthcoming VIROLOGY, occurred in the absence of immune cells, thus adding another dimension to the virus' potential for assisting other pathogens.