How Does HIV Overcome Numerous Obstacles to Infect the Body?

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Researchers analyzed the properties of strains that evade bodily defenses to successfully make the leap from person to person.

January 19, 2017

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The strains of HIV that succeed in establishing an infection through sexual transmission have various properties that facilitate their evasion of the body’s numerous lines of defense against such an invasion.


HIV must first infect a target cell at the initial site of infection, such as the rectum or vagina. Next, the virus needs to travel through the mucus membranes of the genital track and then the tightly packed epithelial cells, which form a barrier against the invasion of pathogens. Then, HIV needs to evade the initial immune response: type-1 interferons, specifically interferon-alpha2 and interferon-beta.


Considering all these obstacles, the per-act chance of transmitting HIV when someone living with the virus has a detectable viral load and ejaculates into the rectum or vagina of an HIV-negative partner is still quite small. (For more information on the quantification of such risks, check out this POZ exclusive.)


Publishing their findings in Proceedings of the National Academy of Sciences, researchers studied 300 viral isolates from the blood and genital secretions of eight HIV-positive individuals and the eight individuals from whom they contracted the virus. They found a subpopulation of HIV strains that had characteristics that made them more likely to efficiently establish new infections.


Compared with the viruses the researchers isolated from the “donor” individuals (the source of the other’s infection), the viruses in the “recipients” were three times more infectious, had a 1.4-fold greater ability to replicate and were more resistant to both types of type-1 interferon.


Compared with the viral isolates from the donors, those isolated from the recipients needed an 8-fold greater concentration of interferon-alpha2 and a 39-fold greater concentration of interferon-beta to halve their replication. In the context of the highest doses of the two type-1 interferons, the interferon-resistant strains of HIV were a respective 35-fold and 250-fold more likely to replicate in CD4 cells nevertheless.


Translation: Strains of HIV that rapidly multiply and are interferon resistant are more likely to transmit, a trait known as increased transmission fitness.


Viral isolates from the recipients emerged from CD4 cells more efficiently than the viral isolates from the donors. This suggested that an important component of the HIV transmission process is the production of new viral particles that have emerged from undetected immune cells.


The study authors concluded that the “mucosal bottleneck” selects HIV strains that are especially potent and insidious, able to copy themselves and spread efficiently through the body despite the immune system’s attack.

The authors say more research is needed to determine which viral genes lead to resistance of interferon and how these genes function. Such scientific understanding could aid in the development of new HIV treatments and prevention methods, including a vaccine.


To read a press release about the study, click here.


To read the study abstract, click here.

  

Read more articles from POZ, here.