Article : "€œZombie"€ HIV Proviruses Revealed!

Rajesh T. Gandhi, MD reviewing Imamichi H et al. Proc Natl Acad Sci U S A 2016 Aug 2.


Presumed “dead” HIV proviruses have been found to express novel RNA transcripts. Might they cause persistent immune activation?

HIV-infected patients on antiretroviral medications with undetectable viral loads continue to have detectable HIV DNA in CD4 cells despite many years of therapy. Previous studies have found that most of that HIV DNA is defective and unable to replicate, a veritable “graveyard” of proviruses. Now, a careful analysis reveals that these defective proviruses may not quite be as “dead” as we thought.

Investigators have now studied HIV DNA proviruses from four patients with undetectable plasma viral loads. As expected, the patients had defective proviruses with deletions or lethal mutations. Surprisingly, when cytoplasmic RNA from these patients was sequenced, the investigators found novel RNA transcripts matching the defective proviruses. These transcripts appeared to be capable of producing viral proteins.


CITATION(S):

Imamichi H et al. Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy. Proc Natl Acad Sci U S A 2016 Aug 2; 113:8783. 

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