A plentiful ingredient found in human semen drastically enhances the ability of the HIV to cause infection, according to team of scientists.
To identify natural agents that might play a role in sexual transmission of HIV/AIDS, the investigators sifted through a peptide/protein library derived from human seminal fluid.
The research team report finding prostatic acidic phosphatase (PAP) fragments as a potent enhancer of HIV infection. They then verified that synthetic PAP fragments also enhanced HIV. The researchers identified that individual PAP fragments are inactive but efficiently form amyloid fibrils, which they call semen-derived enhancer of virus infection (SEVI), that enhance HIV-1 infection by capturing virions and promoting their physical interaction and fusion with target cells including T cells and macrophages.
“We were not expecting to find an enhancer and were even more surprised about the strength,” comments Frank Kirchhoff, Ph.D., of the University Clinic of Ulm and one of the authors. “Most enhancers have maybe a two or threefold effect, but here the effect was amazing—more than 50-fold and under certain conditions, more than 100,000-fold.”
The enhancing activity of SEVI is most pronounced when the levels of infectious virus are low, resembling the conditions of sexual HIV-1 transmission, the scientists explain. SEVI lowered the amount of virus required to infect tissue taken from human tonsils and significantly enhanced the viral infection of transgenic rats with human receptors for HIV-1 infection.
The study was performed by researchers from the University Clinic of Ulm, IPF PharmaCeuticals, Hannover Medical School, VIRO Pharmaceuticals, the University of Heidelberg, and Centro de Investigaciones Biologicas. The results are published in the the December 14 issue of Cell.