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."
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.
The enhancing activity of SEVI is most pronounced when the levels of infectious virus are low, resembling the conditions of sexual HIV-1 transmission, they reported. Physiological concentrations of SEVI amplified HIV infection of immune cells known as T cells and macrophages, most likely the cell types first targeted by HIV-1. 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.
MEDICA.de; Source: Cell Press