A study co-authored by Shilpa Iyer, a doctoral student at the University of Pennsylvania, has identified characteristics of HIV-1 strains that mediate sexual transmission. Upon sexual exposure, the AIDS virus must overcome some mighty barriers to find the right target cell and establish a new infection and must traverse the genital mucosa and squeeze through tightly packed epithelial cells meant to keep invaders out, the study says. And then it must thwart the initial immune-system alarm bell in the form of type 1 interferons. In fact, according to some studies, only about 1 in 1,000 unprotected sexual exposures lead to a successful HIV-1 infection.
“What is unique about these transmitted viruses that make it this far?” asked Beatrice Hahn, MD, a professor of Medicine and Microbiology in the Perelman School of Medicine at the University of Pennsylvania. “The human body has considerable innate barriers that effectively combat virus infections.”
Hahn and colleagues examined the characteristics of HIV-1 strains that were successful in traversing the genital mucosa that forms a boundary to entry by viruses and bacteria. Studying viral isolates from the blood and genital secretions of eight chronically HIV-1 infected donors and their matched recipients, the researchers identified a sub-population of HIV-1 strains with biological properties that predispose them to establish new infections more efficiently. They published their findings online ahead of print this week in Proceedings of the National Academy of Sciences, First Edition.
The team generated 300 virus isolates from individual HIV-1 particles infecting both the donors and their matched recipients. “This means that rapidly multiplying strains of HIV-1 that are interferon resistant have an increased transmission fitness,” the university press release quoted Iyer as saying. “We confirmed this by pretreating CD4 immune cells with interferon prior to virus isolation. In doing this, we were able to select donor isolates that had a transmitted virus-like phenotype.”
The team also showed that recipient isolates were more efficiently released from infected CD4 immune cells than the corresponding donor isolates, suggesting that the production of cell free particles is important in the transmission process.
Overall, the findings show that the “mucosal bottleneck” selects for HIV-1 strains that are able to replicate and spread efficiently in the face of a potent innate immune response.