HIV Latent Reservoir Much Larger Than Thought

Centers for Disease Control and Prevention

The human immunodeficiency virus (HIV) creates a latent reservoir (LR) soon after infecting the host. The reservoir is made up of the cells that are infected with HIV, but do not actively produce the virus. When it is inactive, the virus can hide from antiretroviral treatment (ART), which is why the medications cannot cure a person of HIV. It is possible for cells in the LR to reactivate and being to produce HIV proteins, so it will always pose a threat. A study from Johns Hopkins University School of Medicine published 24 October 2013 in Cell has shown that the LR is 60 times larger than previously thought and does not behave predictably. This presents new challenges to researchers developing medications.

 

There are two ways to detect LR: polymerase chain reaction (PCR) and viral outgrowth assay (VOA). HIV DNA that is nonfunctioning in the cell is amplified with PCR so that researchers can count it. VOA works by forcing the dormant virus cells to reactivate and produce HIV proteins, which can then be measured.

 

This study combined both techniques by first inducing cells from the LR, and then using PCR on the rest to see what the first technique may have missed. It turns out, VOA misses a lot. Not all of the cells that have been made to reactivate actually do the first time around.

 

Of the cells that did not reactivate after the first round of treatment, 88% of them would not be able to function anyway due to mutations that left them defective. The other 12% of the HIV DNA that didn’t activate did not have any defects and should function normally. Researchers are having a difficult time understanding why those cells did not respond, and have concluded that cell reactivation must be random. They also determined the number of cells in the LR is 60 times greater than previously believed. 

 

While these results are interesting, it presents a severe problem in the treatment of the virus: If the cells cannot be induced to produce protein, ART cannot find and attack the virus. If the virus stays hidden in the LR, there is always a possibility for it to come back.

 

These results might sound disheartening at first glance. However, having a clear, accurate picture of the problem at hand will allow researchers to better understand virus latency so more efficient treatments can be developed.

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