Defective copies of HIV that are integrated into long-living immune cells distract the immune system, complicating the effort to track down and kill viable copies of the virus. This finding identifies yet another hurdle to finding effective therapies to clear the viral reservoir and ultimately cure HIV.
When HIV infects an immune cell, the virus integrates its genetic materials into the cell’s own DNA, yielding what is known as an HIV provirus. However, the majority of proviruses cannot produce new, intact copies of HIV because of flaws in the reproduction process. Consequently, until recently, researchers believed that proviruses amounted to a biological dead end and that cells latently infected (meaning they are not replicating and are therefore invisible to standard HIV treatment) with defective provirus could not prompt a repopulation of the virus in the body.
Publishing their findings in Cell Host & Microbe, scientists studied memory CD4 cells drawn from HIV-positive individuals as well as reconstructed defective proviruses drawn from people with HIV. Latently infected memory CD4 cells, which can live a very long time, are a major component of the viral reservoir, the presence of which frustrates attempts to cure the virus.
The investigators concluded that the presence of the defective proviruses promotes the survival of the overall HIV infection by serving as a decoy. The immune system, recognizing the viral proteins that serve as signs of infection in the cells infected with defective proviruses, wastes resources attacking those cells.
In its effort to seek out and destroy proviruses, the immune system is confronted with a needle-in-a-haystack effort because people with HIV have about 1,000 times more defective proviruses than viable ones, and the immune system apparently cannot detect the difference between them.
This decoy effect also complicates the effort to measure the viral reservoir because most current tests also cannot distinguish between defective and viable provirus.
To read a press release about the study, click here.
To read the study abstract, click here.