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Campus Currents May 2007: Volume 4, Number 2

HIV, the Alzheimer's Clue

Scientists had suspected that something in semen enhanced the transmission of HIV to sexual partners. Three years ago, they found it—a protein superstructure that attracts the virus and deposits it on the surface of immune cells. Now chemists at UC San Diego have synthesized a drug candidate that disrupts that delivery and dramatically lowers the rate of infection of cultured cells.

The protein culprit, called SEVI for semen-derived enhancer of viral infection, assembles from short pieces to form fibrous mats and strings called amyloid. A similar protein structure, amyloid beta, forms the pathological plaques found in the brains of people with Alzheimer's disease.

That gave Alzheimer's researcher Jerry Yang an idea. His group has been taking a new approach to the treatment of Alzheimer's disease. Instead of trying to bust up the amyloid plaques, they have been covering amyloid with a non-stick coating meant to thwart its harmful interaction with the brain.

Yang thought one of the drug candidates they were synthesizing to treat Alzheimer's might effectively reduce HIV infection by disabling the amyloid found in semen. So he teamed up with HIV researchers at the University of Rochester Medical Center to test the concept and found that it worked.

When the researchers mixed Yang's drug candidate with SEVI (isolated from semen), virus and immune cells, the rates of infection dropped to levels observed when SEVI was absent.

"Other people have tried to do the same thing by targeting the virus or the cells it infects. What we do is target the mediator between the virus and the cells," Yang says. "By neutralizing SEVI, we prevent at least one way for HIV to attach to the cells."

They saw a similar effect with whole semen including SEVI as well, evidence that the coating could inhibit infection within the normal stew of proteins and other molecules found in seminal fluid. Unlike other potential anti-virals, the molecule that Yang's group has made doesn't inflame cervical cells, making it a promising potential ingredient for a gel or foam designed to limit sexual transmission of HIV.

—Susan Brown