Washington, Dec 14 : Scientists have identified a protein in human semen that increases the risk of HIV infection up to 100,000-fold.
Scientists have identified a protein in human semen that increases the risk of HIV infection up to 100,000-fold.
German researchers at the University Clinic of Ulm have found an ingredient in human semen that may actually help the HIV virus infect cells.
They say that their finding could shed more light on the sexual transmission of HIV and provide new drug targets and strategies for combating the global AIDS epidemic.
The team screened a library of peptides and discovered that fragments from prostatic acidic phosphatase (PAP), an enzyme abundant in semen, boosted the chances of cells becoming infected with the HIV virus. The enzyme forms tiny clumps of insoluble fibres - which the researchers named Semen-derived Enhancer of Virus Infection (SEVI) - that capture virus particles and ferry them straight into cells.
'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,' said Frank Kirchoff, who led the research at the University Clinic of Ulm, Germany.
"The fibrils act like a ferry. They pick the viruses up and then bring them to the cell," said Wolf-Georg Forssmann of VIRO PharmaCeuticals GmbH and Co. KG and Hannover Medical School.
The HIV virus, which is the causative agent of AIDS, has infected about 60 million people worldwide, the majority caused by unprotected sexual intercourse. However, despite its widespread nature, the sexual route of contraction is relatively inefficient - it has been estimated that the chance of HIV transmission via male-to-female sexual intercourse is about 1 in 200.
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.
The researchers said they would continue to explore SEVI's role in HIV transmission. While the peptide that conglomerates into fibrils is always present in large quantities in semen, they don't yet know if the absolute levels vary from man to man.
"We also plan to further explore how exactly the fibrils allow the virus to enter cells and to search for compounds, with our technology, that might block the process," Forssmann said.
Kirchhoff said that if such inhibitors can be found, they might be added to microbicide gels now under development for HIV prevention.
"The high potency of SEVI in promoting viral infection together with its relatively low cytotoxicity suggests that it may not only play a relevant role in sexual HIV transmission, but could also help to improve vaccine approaches and gene delivery by lentiviral vectors," the researchers said.
The study is published in the journal Cell, a publication of Cell Press. (ANI)
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