Scientists identify human proteins that may fuel HIV/AIDS transmission

December 14, 2011
Amyloid fibrils in semen, shown here in red, enhance HIV infection by helping HIV -- shown in green -- find and attach to its target, CD4 T white blood cells. Credit: Nadia Roan/Gladstone Institutes

Scientists at the Gladstone Institutes have discovered new protein fragments in semen that enhance the ability of HIV, the virus that causes AIDS, to infect new cells -- a discovery that one day could help curb the global spread of this deadly pathogen.

HIV/ has killed more than 25 million people around the world since first being identified some 30 years ago. In the United States alone, more than one million people live with HIV/AIDS at an annual cost of $34 billion.

Previously, scientists in Germany discovered that is linked to the presence of an amyloid fibril in semen. This fibril -- a small, positively charged structure derived from a larger protein -- promotes by helping the virus find and attach to its target: CD4 T white blood cells. In tomorrow's issue of Cell Host & Microbe, researchers in the laboratory of Warner C. Greene, MD, PhD, who directs virology and immunology research at Gladstone, describe a second type of fibril that also has this ability.

These findings may spur efforts to slow the spread of HIV/AIDS. Prevention has recently focused on microbicides; chemical gels that, when used by women during sexual intercourse, block HIV infection. But while early microbicides had some success -- reducing infection by an average of 39%—more recent trials have failed and devising a truly potent microbicide remains a top priority.

"Today's microbicides may be failing because, while they do target the virus itself, they don't block the virus from interacting with the natural infection-enhancing components of semen," said Nadia R. Roan, PhD, the paper's first author and a research scientist at Gladstone, an independent and nonprofit biomedical-research organization. "Now that we more fully understand how HIV hijacks these components to promote its own infection, we are one step closer to developing a microbicide that can more effectively stop HIV."

Sexual transmission accounts for the vast majority of HIV infections, and semen is the virus' key mode of transport. Earlier studies by Drs. Roan and Greene revealed the mechanism by which a positively charged fibril in semen -- called SEVI -- attracts HIV like a magnet, binding to the negatively charged HIV and helping to infect CD4 T cells. Here, they set out to investigate whether other components of semen also played a part.

In laboratory experiments on human semen samples, they identified a second set of fibrils -- derived from larger proteins called semenogelins -- that enhance HIV infection just as SEVI does. Removing these and other positively charged components from semen diminished HIV's ability to infect CD4 T . Further confirming the role of these fibrils in promoting HIV infection, Drs. Roan and Greene found that semen samples from men who are naturally deficient in semenogelins -- a disorder called ejaculatory-duct obstruction -- also had a limited ability to enhance HIV infection.

"Our experiments suggest that fibrils derived from semenogelins -- the major component of semen -- are integral to enhancing infection in ," said Dr. Roan. "But we are intrigued by their natural, biological function as well. The fact that these fibrils are found in male reproductive organs could point to an evolutionary role in fostering fertilization -- something we're currently exploring."

"We hope that this research paves the way for the next-generation of microbicides that can both neutralize these fibrils and attack the ," said Dr. Greene, who is also a professor of medicine, microbiology and immunology at the University of California, San Francisco, with which Gladstone is affiliated. "This type of one-two punch in a microbicide -- what current products lack -- could finally give women real protection against HIV's deadly attack."

Related Stories

Recommended for you

New injectable antiretroviral treatment proved to be as effective as standard oral therapy

August 3, 2017
Intramuscularly administered antiretroviral therapy (ART) may be as effective for HIV treatment as current oral therapies. This is the main conclusion of a Phase II clinical trial carried out by 50 research centers around ...

Research finds home-based kit would increase HIV testing

July 31, 2017
Research led by William Robinson, PhD, Associate Research Professor of Behavioral & Community Health Sciences at LSU Health New Orleans School of Public Health, has found that 86% of heterosexuals who are at high risk for ...

Scientists divulge latest in HIV prevention

July 25, 2017
A far cry from the 1990s "ABC" campaign promoting abstinence and monogamy as HIV protection, scientists reported on new approaches Tuesday allowing people to have all the safe sex they want.

Girl's HIV infection seems under control without AIDS drugs

July 24, 2017
A South African girl born with the AIDS virus has kept her infection suppressed for more than eight years after stopping anti-HIV medicines—more evidence that early treatment can occasionally cause a long remission that, ...

Meds by monthly injection might revolutionize HIV care (Update)

July 24, 2017
Getting a shot of medication to control HIV every month or two instead of having to take pills every day could transform the way the virus is kept at bay.

Candidate AIDS vaccine passes early test

July 24, 2017
The three-decade-old quest for an AIDS vaccine received a shot of hope Monday when developers announced that a prototype triggered the immune system in an early phase of human trials.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.