New Insights Into Hidden Reservoirs for HIV Infection

By Jeffrey Laurence, M.D.

November 2011 - One major impediment to a cure for AIDS is the long-lived reservoir of latently HIV-infected cells. Virus in such cells, predominantly central memory T cells, is resistant to all known anti-HIV drugs. And yet,

Dr. Alberto Bosque

upon activation, viral growth is rapidly induced and spreads to infect other cells. Dr. Alberto Bosque, an amfAR Mathilde Krim Fellow working at the University of Utah, is exploring the signals required for activating such latently infected T cells and the virus within them, with the goal of regulating both processes.

Writing in the October issue of the science journal PloS Pathogens, Bosque and his colleagues from Utah and Milan address a key question in the biology of HIV latency: How can such cellular reservoirs be maintained if, by activating such cells, virus is also activated and ultimately kills the reservoir cells? In a challenge to accepted wisdom, Bosque demonstrates that a resting cell state is not an absolute requirement for maintaining viral latency. Certain normal immune hormones, including IL-2 and IL-7, enable these cells to proliferate without activating the virus. This process could maintain latent virus, along with its host memory T cells, for a very long period of time.

In contrast, stimulating such latently infected cells with a foreign antigen—another infection, for example—activates both the cell and its virus, leading to death of the cell by virus-associated killing.

These types of observations are important in the evaluation of potential “shock and kill” strategies designed to reduce the latent reservoir through simultaneous activation of cell growth and viral growth. Bosque concludes by stating that such “potential ‘anti-latency’ drugs should be examined for the undesired ability to induce cellular proliferation in the presence of incomplete viral reactivation.”

Dr. Laurence is amfAR’s senior scientific consultant.