Why HIV Genetic Diversity Varies Between Vaginal Tract, Blood Stream

Samples of the female genital tracts of women infected with HIV show that the virus loses much of its genetic diversity by the time it hits the bloodstream.

Eric Arts, PhD

New research suggests HIV-1 loses some of its genetic diversity as it travels from the vaginal tract to the bloodstream in women who contract the virus through intercourse.

The findings have significant implications for how researchers think about the disease, and affirms the theory that a sort of “bottleneck” essentially strains out some variants of HIV-1 between initial transmission and the time the virus enters the bloodstream.

Eric Arts, PhD, chair of the department of microbiology and immunology at Western University, in Canada, has been studying a cohort of HIV-infected women for more than a decade, first at Case Western University, and now at Western University. Partnering with a research center in Uganda, Arts and colleagues tracked about 300 HIV-infected women for an average of 7 years. The data have led to a series of studies.

For this paper, Arts said researchers faced a difficult problem in trying to measure genetic diversity at infection. It wouldn’t be feasible or ethical to collect donor semen samples from male subjects during transmission, so instead the team focused on female subjects. In the early 2000s, they began collecting samples from newly infected women’s vaginal tracts, along with blood samples.

“For over 10 years, we attempted to analyze these cervical samples but were always plagued by the limitation in sample quantity and in technology,” Arts told MD Magazine. “Starting around 2014, we finally had a next-generation protocol along with the bioinformatic algorithms to finally tackle this important question.”

That protocol enabled the researchers to discover that the virus found in the vaginal tract had an average of 5.7 genetic variants of HIV-1, while the virus in the blood of the same patients had an average of just 1.7 genetic variants. Those figures were not affected by HIV-1 subtype, use of contraceptives, or number of sex acts or partners. The samples came from 75 women in Uganda and Zimbabwe, and all were taken within 7 months of infection.

Arts noted that their measurements of vaginal tract diversity could be low, since the swabs they used to collect cervical samples only resulted in samples of 1% or 0.1% of the vaginal tract.

“It is quite possible the HIV genetic diversity may have been even higher if we had obtained and tested a lavage from the FGT (female genital tract),” he said.

Now that they know about the shedding of genetic diversity, Arts and colleagues are already working to try to apply the new knowledge toward the goal of stopping transmission. In another forthcoming study, Arts worked with Robin Shattock, PhD, of Imperial College London, to try and decipher which traits make a particular HIV-1 variant capable of getting past the body’s defenses and causing transmission.

“We now have strong evidence that a pool of HIV-1 strains may infect this human mucosal tissue (e.g. in the FGT) during transmission but that only a few HIV-1 clones (in the infecting population in the FGT) have the required properties to ‘break’ this mucosal trap,” he said.

If Arts can figure out what makes some variants able to escape the mucosal trap, does that mean it might be possible to create a vaccine to target those variants’ ability to successfully pass through the vaginal tract? Potentially, Arts said. He can’t go into detail yet as his research on that question has yet to be published. However, Arts suggested that that strategy would be just as difficult as it is intriguing.

“From what I know, it will not be easy to change the microenvironment, but I suspect that microbiome/muscosal constituents may play a key role in defining transmission efficiency of the clones with ‘high transmission efficiency’ from the FGT to the blood,” he said.

Another big question, Arts said, is whether that scenario already happens naturally in some women; meaning, the virus is transmitted but it essentially burns out before it can seroconvert and cause systemic infection.

That’s pure conjecture at this point, Arts said, but it’s a question he’s “extremely curious” to explore. There has been little research on the question to date, he said.

One study did suggest that remnants of HIV-1 were present in the vaginal tracts of some HIV-negative women.

“We have talked about testing their FGT samples but as in all studies, these are few and far between,” he said. “Pity because this info may hold the key to preventing transmission.”

Arts’ study on genetic diversity during transmission was published today in PLOS Pathogens. It can be read in full at this link.

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