Semen boosts HIV transmission

Fibres may be more important than viral load in determining transmission rates.

A component found in semen can enhance HIV transmission by as much as 100,000-fold, researchers have found. The results, if verified in a clinical setting, could identify a new way to help prevent the spread of the disease.

"I think this is tremendous," says Christopher Pilcher, an HIV researcher at the University of California, San Francisco, who was not affiliated with the study. "It raises a lot of really fundamental questions about how HIV is transmitted."

Over 80% of HIV infections are acquired through sexual intercourse, primarily via semen from HIV-positive men. Pilcher says that researchers have been studying the role of semen in HIV transmission, but have focused primarily on the quantity and type of virus contained in semen. "We’ve looked at everything except the semen itself," he says.

Now researchers have found that peptides clustered together into long fibres may be more important for HIV transmission than viral load. “If that’s true, then we’ve been looking at the wrong thing for a long time,” says Pilcher.

Helping to infect ourselves

The fibres are the latest in a growing list of products produced by the body that affect HIV infection. Earlier this year, Frank Kirchhoff of the University of Ulm in Germany, together with Wolf-Georg Forssmann of IPF PharmaCeuticals in Hannover, Germany, and their colleagues, reported the isolation of a peptide found in blood that inhibits HIV entry into cells.

Now, Kirchhoff and Forssmann have taken a similar approach using semen. They collected peptides and small proteins harvested from semen and then screened the compounds in cell cultures to determine the effects on HIV infectivity.

They found that fragments of a protein called 'prostatic acidic phosphatase' strongly enhanced HIV transmission. The peptides were most active when they clustered together to form fibres called amyloid fibrils.

Depending on the laboratory assay being used, the fibres enhanced transmission of the virus by as little as 30-fold or as much as 400,000-fold. The results are published this week in Cell ¹. The researchers also tested the fibres in rats that were engineered to be susceptible to HIV infection. Rats injected with both the fibres and HIV had five times more viral DNA in their blood than those injected with HIV alone.

Seminal fibres

Many human proteins can form amyloid fibrils, and these fibres are associated with several diseases including Alzheimer’s disease, Parkinson’s disease and diabetes. But none had been previously shown to affect virus transmission, says Per Westermark, who studies the fibrils at Uppsala University in Sweden.

The seminal fibres physically capture the HIV virus, the researchers found, and help HIV to interact with host cells in culture. This suggests that drugs that prevent HIV from binding to the fibres could slow HIV spread, says Westermark.

Robin Shattock, an HIV researcher at St. George's, University of London, who has also been studying HIV transmission, says the results are promising but cautions against reading too much into them without additional clinical studies. The researchers performed many of their experiments with purified peptide, he notes, which may not behave in the same way that it would in unmodified semen.

“The definitive experiments have not been done,” says Shattock. Shattock argues that the peptide fibres need to be tested in a non-human primate by exposing mucosal surfaces to HIV in the presence or absence of semen. Meanwhile, Pilcher estimates that clinical studies in humans could evaluate the relationship between seminal peptide-fibre content and HIV transmission within the next few years.

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