A plentiful ingredient found in human semen drastically enhances the ability of the human immunodeficiency virus (HIV) to cause infection, according to a report in the December 14, 2007, issue of the journal Cell, a publication of Cell Press.
The findings help to understand the sexual transmission of HIV and suggest a potential new target for preventing the spread of AIDS, the researchers said.
Collaborating research groups in Hannover and Ulm, Germany, show that naturally occurring fragments of so-called prostatic acidic phosphatase (PAP) isolated from human semen form tiny fibers known as amyloid fibrils. Those fibrils capture HIV particles and help them to penetrate target cells, thereby enhancing the infection rate by up to several orders of magnitude.
"We were not expecting to find an enhancer, and were even more surprised about the strength," said Frank Kirchhoff of the University Clinic of Ulm, noting that they were initially looking for factors in semen that might help to block HIV infection. "Most enhancers have maybe a two- or three-fold effect, but here the effect was amazing—more than 50-fold and, under certain conditions, more than 100,000-fold. At first, I didn't believe it, but we ran the experiment over and over, always with the same result."
"The fibrils act like a ferry," said Wolf-Georg Forssmann of VIRO PharmaCeuticals GmbH & Co. KG and Hannover Medical School. "They pick the viruses up and then bring them to the cell."
HIV-1, the causative agent of AIDS, has infected about 60 million people and caused over 20 million deaths, the researchers said. More than 90 percent of those HIV-1 infections are acquired through sexual intercourse. Globally, most infections result from genital exposure to the semen of HIV-positive men, earlier studies showed. Women who acquired HIV-1 through vaginal intercourse constitute almost 60 percent of new infections in Africa. Yet the factors influencing the infectiousness of HIV in semen are poorly understood.
To identify natural agents that might play a role in sexual transmission of HIV/AIDS in the new study, the researchers sifted through a complex peptide/protein library derived from human seminal fluid in search of novel inhibitors and/or enhancers of HIV infection.
That comprehensive search turned up PAP fragments as a potent enhancer of HIV infection. They then verified that synthetic PAP fragments also enhanced HIV, confirming it as the active ingredient. Interestingly, they found that individual PAP fragments are inactive but efficiently form amyloid fibrils, which they call Semen-derived Enhancer of Virus Infection or SEVI, that enhance HIV-1 infection by capturing virions and promoting their physical interaction and fusion with target cells.