More than 80 percent of human immunodeficiency virus (HIV) infections are transmitted via sexual intercourse. And researchers may have discovered atleast one reason why.
According to a new study published in Cell, a component of human semen may facilitate the spread of the virus by targeting immune system cells, in some cases making the pathogen upto 1,00,000 times more virulent.
An ingredient in human semen may actually help the HIV virus infect cells, German researchers informed.
They said naturally occurring prostatic acidic phosphatase or PAP, an enzyme produced by the prostate, can form tiny fibres called amyloid fibrils that can capture bits of the human immunodeficiency virus and usher it into cells.
Researchers at the University Clinic of Ulm were looking for factors in semen that might block infection with HIV-1, the most common strain of the virus that causes AIDS. Instead, they found one that enhanced transmission, in some experiments as much as 50-fold.
"In this study we show that fragments of PAP, a highly abundant semen marker, forms amyloid fibrils that drastically enhance the infectiousness of HIV-1," they wrote in the journal Cell .
They said they are now looking for compounds that might block this process to slow transmission of the disease.
Amyloid fibrils formed from different proteins are associated with many diseases, including Alzheimer’s and prion disease.
"Further studies on the role of amyloids in the transmission and pathogenesis of enveloped viruses are highly warranted," they wrote.
HIV has infected some 60 million people, killing more than 20 million, the researchers said. More than 90% of those infections are acquired through sexual intercourse.
The transmission rate from intravaginal sexual intercourse is estimated at one in every 200 to 2,000 acts. . In Africa, 60 percent of new infections are in women who have had sex with HIV positive men.
Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk. Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells. The four major routes of transmission are unprotected sexual intercourse, contaminated needles, and transmission from an infected mother to her baby at birth, or through breast milk.
Screening of blood products for HIV in the developed world has largely eliminated transmission through blood transfusions or infected blood products in these countries.
Kirchhoff and his team screened through many of the 900 proteins found in seminal fluid in their hunt for potential inhibitors and enhancers of HIV transmission. Among the enhancing factors uncovered were fragments of a protein called prostatic acid phosphatase that is secreted by the prostate gland.
An analysis of the peptide’s structure in semen indicated that it hooked up with similar fragments to create amyloid fibers (clusters of protein fragments that have also been implicated in diseases such as Alzheimer’s). The scientists refer to the amyloid fibers as "semen-derived enhancer of virus infection" (SEVI).
If they do not link to become fibers, the researchers report, the peptide segments remain inactive and do not enhance viral transmission. When assembled, however, these fibers then act like ferries, trapping and shuttling HIV virus particles to target cells.
The researchers found that HIV spiked into semen was more successful than the virus alone at infecting T cells and macrophages (immune system cells that are believed to be the infection’s initial targets in the body). They also tested the threshold of virus needed to infect human tonsil cells, noting that in the presence of semen, far fewer HIV particles were needed for transmission.
Researchers injected both the naked virus and SEVI-treated HIV into the tails of rats that had been given human immune system cells. The HIV with the semen component was five times more effective at transmitting the virus.
In situations where low levels of virus are transferred—as during intercourse—Kirchhoff says, SEVI can make HIV up to 100,000 times more likely to spread when compared with the virus alone.
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