amfAR, The Foundation for AIDS Research

Potential New Targets to Block HIV Latency

Jeffrey Laurence, M.D.

Dr. Sharon LewinDr. Sharon LewinIt’s been known for over two decades that HIV establishes a dormant, or latent, state in CD4+ T cells, in which virus is impervious to the effects of currently available antiretroviral therapies (ART). Multiple subtypes of these T cells can similarly harbor HIV, but it had been assumed that HIV latency occurred when these cells reverted from an activated state to a resting state. Infection of actively growing, proliferating cells was thought to favor productive over latent viral states.

But in a recent issue of the Journal of Immunology, amfAR-funded scientist Sharon Lewin and her colleagues demonstrate that HIV latency can indeed be maintained in actively growing cells. The researchers suggest that this finding may open new avenues to abolish latency.

Lewin and associates used a novel test-tube model, which the team developed, to study the establishment of the HIV reservoir in active and resting CD4+ T cells, simultaneously. The team found that latency was established in both types of T cells but by distinct mechanisms. HIV latency preferentially occurred in a portion of resting T cells through a prolonged interaction with a second cell, the myeloid dendritic cell (mDC).  

Unexpectedly, they found a greater frequency of latent infection in active rather than resting T cells. The active cells bore large amounts of PD-1, a so-called immune checkpoint protein. Blocking its activity is the focus of several new “miracle” anti-cancer drugs, which work for some patients when chemotherapy has failed.

The authors conclude that the means by which HIV induces latency in T cells, and thus evades current cure strategies, may be dependent on interactions with other immune cells such as mDC and immune checkpoint proteins. Overcoming latency therefore “may require targeted therapeutic strategies.”

Dr. Laurence is amfAR’s senior scientific consultant.