What does it take for an AIDS virus to infect a person?

January 10, 2017
HIV infecting a human cell. Credit: NIH Image Gallery

Upon sexual exposure, the AIDS virus must overcome some mighty barriers to find the right target cell and establish a new infection. It must traverse the genital mucosa and squeeze through tightly packed epithelial cells meant to keep invaders out. 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. Compared to viruses isolated from the donors, they found that recipient viruses were three times more infectious, had a 1.4 higher ability to replicate, and were significantly more resistant to the antiviral effects of two type 1 interferons, IFN-alpha2 and IFN-beta. Compared to the donor isolates, transmitted viruses required eight-fold higher concentrations of IFNalpha2 and 39-fold higher concentrations of IFN-beta to achieve a 50 percent reduction in replication. In addition, the odds of the interferon-resistant strains replicating in CD4 —the main targets of HIV-1—at the highest IFN-alpha2 and IFN-beta doses were 35-fold and 250-fold greater, respectively. Interferons are proteins released by immune cells in response to foreign pathogens—viruses, bacteria, parasites, and also tumor cells.

"This means that rapidly multiplying strains of HIV-1 that are interferon resistant have an increased transmission fitness," said Shilpa Iyer, a doctoral student in the Hahn lab and a co-first author of the study. "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 . "Knowing the viral properties that confer the ability to transmit despite all of the human body's barriers to infection, might aid the development of vaccines against HIV-1," Hahn said. "But we still don't know which viral gene products render HIV-1 resistant to interferon and how they function. The next steps will be to dissect these mechanisms to define possible new targets for AIDS prevention and therapy."

Explore further: Researchers find how Ebola disables the immune system

More information: Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1620144114

Related Stories

Research deciphers HIV attack plan

April 1, 2013

(Medical Xpress)—A new study by Los Alamos National Laboratory and University of Pennsylvania scientists defines previously unknown properties of transmitted HIV-1, the virus that causes AIDS. The viruses that successfully ...

Which interferons best control viral infections?

June 26, 2014

Respiratory and intestinal infections caused by RNA viruses stimulate infected cells to produce interferons, which can act alone or in combination to block virus replication. Important differences between the presence of ...

Recommended for you

What does it take for an AIDS virus to infect a person?

January 10, 2017

Upon sexual exposure, the AIDS virus must overcome some mighty barriers to find the right target cell and establish a new infection. It must traverse the genital mucosa and squeeze through tightly packed epithelial cells ...

S.Africa launches major new trial of AIDS vaccine

November 29, 2016

South Africa on Wednesday launched a major clinical trial of an experimental vaccine against the AIDS virus, which scientists hope could be the "final nail in the coffin" for the disease.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

samuellughano
not rated yet Jan 18, 2017
Hello friends, am Anthony Maqebelo by name, i was one of those millions of people living with HIV, i received my breakthrough with the help of Dr Olumo whom i met through the testimony of someone he has helped, after some series of conversation with the person sharing the testimony i decided to contact Dr Olumo which i did, after some negotiation he sent me the medicine with an instruction on how to use it, i notice some change in my body when using the medicine, after completing the dose as instruct i went for test only to be confirm negative by the doctor after the result came out, words on the internet can not express it all, if you are in the same condition and you are looking for a way out of it you can contact Dr Olumo on his email address, doctorolumo@gmail.com, or you can call or whatsapp via +2348138956767.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.