Target May Inhibit HIV Infectivity

Scientists at the Gladstone Institute of Virology and Immunology have discovered an agent that might inhibit the infectivity of HIV. The agent, surfen, impairs the action of a factor in semen that greatly enhances the viral infection. Surfen might be used to supplement current HIV microbicides to greatly reduce HIV transmission during sexual contact.

The discovery was made by Nadia Roan, Ph.D., a senior fellow in the laboratory of GIVI director Warner Greene, MD, Ph.D.

Surfen is a small molecule that inhibits the actions of certain polysaccharide molecules called heparan sulfate proteoglycans, which are found on the surface of cells. Importantly for HIV infection, it also interferes with the action of semen-derived enhancer of viral infection. The discovery was published in the current issue of the Journal of Biological Chemistry.

"Surprisingly, although HIV readily replicates once inside the body, the virus struggles to establish a beachhead of infection during sexual transmission," says Greene, who is senior author of the study. "We have been studying SEVI, a naturally occurring factor present in semen that can make HIV thousands of times more infectious. Knowing more about surfen, a SEVI inhibitor, might enable us to lower transmission rates of HIV."

SEVI is a breakdown product of prostatic acid phosphatase, a common protein in semen. Under certain conditions, SEVI can increase HIV infectivity 100,000 times by facilitating the attachment of viruses to target cells. Because the majority of all HIV infections are thought to result from sexual contact (during which semen is either the vehicle carrying HIV or is present during the infection process), SEVI might have a significant impact on HIV transmission rates. Surfen interferes with the binding of SEVI to both target cells and HIV-1 virions but does not cause the SEVI fibrils to break up.

"Because SEVI can so greatly enhance HIV infectivity, supplementing current HIV microbicide candidates with SEVI inhibitors, such as surfen, might increase their potency and overall effectiveness," Greene explains.