Jan Munch and Shariq Usmani (right) in their lab and (below) 3D reconstruction of amyloid in semen (red) interacting with virus particles (green)

Clumps of protein fragments that increase the infectiousness of the human immunodeficiency virus (HIV) by up to a whopping thousand-fold are naturally present in human semen, a team of researchers in Germany has shown.

These findings have, in a way, put the lid on a controversy that erupted in 2007 when researchers — including the lead author of the current study, Jan Munch of Ulm University Medical Center (UUMC) in Germany — found that lab-bred protein clumps could help boost the infection rate of the virus. Critics however dismissed its relevance then saying there is no proof that they are naturally present in semen.

“For the first time it’s been shown that amyloid fibrils (protein fragments) are naturally present in semen. It seems that HIV has hijacked these fibrils to boost its ability to infect,” says Shariq Usmani, postdoctoral fellow at UUMC and the first author of the paper which appeared in the journal Nature Communications early this month. Usmani hails from Azamgarh in Uttar Pradesh.

In the 2007 study the scientists were caught by surprise that these protein fragments — called amyloid fibrils by the scientists — increased the infection rate by several order of magnitude. This prompted them to repeat the laboratory experiment several times, each time with similar results.

Though these amyloid fibrils, quite similar to senile plaques implicated in Alzheimer’s and other neurodegenerative disorders, were shown up in the lab tests, scientists were not sure whether they are formed naturally.

There has been a spurt in research on amyloid fibrils — also called Semen-derived Enhancer of Viral Infection (SEVI) — subsequently, but its critics argued that these substances are not physiologically relevant as it has not been proved that they are naturally present in semen. The new study is significant because it indicates that the amyloid fibrils could emerge as a potential target for microbicides, which are used as vaginal gels to prevent the transmission of HIV.

In the 30-odd years since it was discovered, HIV/AIDS has killed nearly 30 million people worldwide. Nearly 33 million people currently live with the infection, a sizeable proportion of them in sub-Saharan Africa.

“Despite its dramatic spread in the human population, HIV is rather a clumsy virus when it comes to transmission of the infection. It takes anywhere between 200 and 2,000 coital acts for each heterosexual transmission of the infection to happen,” says Usmani. However, this rate of infection increases ten-fold when there is an acute infection, he says.

Still, sexual intercourse is responsible for nearly 80 per cent of HIV infections.

For the study, the scientists examined the ejaculate from 30 healthy men of different ages. “We found that the fibrils are present in all the samples, though their quantity differed. But the fewer the numbers, the bigger the fibrils,” says Usmani who attended Aligarh Muslim University and Jawaharlal Nehru University in New Delhi.

“It is as if these superstructures form a fishnet-like mat which captures the virus and delivers it to the target cells,” says Usmani, explaining the mechanism.

“This is a valuable finding. It always amazes me to see how many tricks a virus like HIV has up its sleeves. This work enhances our knowledge of how HIV ensures its own success by exploiting the cellular machinery at multiple levels,” says Udaykumar Ranga, professor of molecular biology and genetics at the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) in Bangalore.

Semen is known to contain many additional components that improve HIV stability and even enhance its infectivity, says Ranga.

“All the previous publications and the present one demonstrated the enhanced viral infectivity only in laboratory settings. It is still necessary to prove that all these components in the fluid are indeed of biological consequence in the natural context and enhance viral infectivity. This is not a simple task,” remarks the JNCASR professor.

Despite the presence of the infection-enhancing factors in semen, the real rate of viral transmission is very, very low in the natural context. Alternatively, it is possible that HIV is actually transmitted at a much higher rate than what we see but the immune system and its components do not permit easy colonisation. “The findings of the present publication become important if this is indeed the case,” says Ranga.

The JNCASR professor says he is not quite convinced this finding can lead to an effective control measure. “Most of the microbicides haven’t been successful despite demonstrated merits in the laboratory. Whether the amyloid fibrils are of any biological importance in the natural context has not been demonstrated,” he says.

Usmani, on the other hand, says most microbicides in use currently target the virus and many of them are very toxic. “If we can target compounds like fibrils that the virus hijacks to boost its infectivity, we could bring down infection rates further,” says Usmani who now plans to embark on research to identify what role these amyloid fibrils play in normal semen.