amfAR, The Foundation for AIDS Research

Self-Sustaining Reservoirs of HIV

By Jeffrey Laurence, M.D.


Last month we described the efforts of amfAR-funded scientists to uncover novel means of destroying the silent or latent reservoir of HIV that persists in memory CD4+ T cells—the major obstacle to a cure. This month three amfAR grantees, Drs. Ann Chahroudi and Guido Silvestri of the Yerkes National Primate Research Center in Atlanta, Georgia, and Dr. Mathias Lichterfeld of Massachusetts General Hospital, pursue another component of this obstacle: the self-perpetuating memory stem cell.  

Dr. Ann ChahroudiDr. Ann ChahroudiWriting in the March issue of Current HIV/AIDS Reports, Drs. Chahroudi, Silvestri, and Lichterfeld, note that just as every cell in the body is derived from stem cells capable of differentiating into their mature progeny, T cells also have precursor stem cells. These T stem cell memory cells, TSCM, are fairly common, making up about one in every 25 T cells circulating in the blood. And they appear to have a potent dual role when it comes to HIV, acting to both combat the virus and contribute to its persistence.  

On one hand, the researchers found that higher levels of the TSCM that ultimately become CD8+ T killer cells predict lower levels of HIV in untreated patients. In addition, monkeys resistant to the pathologic effects of the simian AIDS virus, SIV, have TSCM resistant to infection. On the other hand, they report that TSCM that will eventually become the critical CD4+ T cell in humans are able to be infected by HIV. In other words, the T cells may become (and remain) HIV-infected very early in their maturation process. And because they have stem cell characteristics, they may be able to perpetuate HIV persistence indefinitely through self-renewal and continuous differentiation into mature memory T cells.  

Dr. Chahroudi presented her findings at a small think tank hosted by amfAR in mid-March in Las Vegas, Nevada. It was a session involving a dozen scientists, including active AIDS researchers and immunologists from other fields with important information to share about attacking this issue. So we have yet another avenue to explore in the search for an HIV cure.  

Dr. Laurence is amfAR’s senior scientific consultant.

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