How HIV Establishes Its Reservoirs

The vast majority of these updates have described methods for eliminating the primary barrier to a cure: the latent reservoir of HIV that persists in infected individuals despite receiving antiretroviral therapy. Now an international team of researchers reports a major new finding on how this reservoir is actually formed, and what it implies for cure strategies.

Dr. Liang Shan

Dr. Liang Shan

The research was reported in the October issue of the journal Immunity by Dr. Liang Shan, an amfAR Mathilde Krim Fellow working in the laboratory of Dr. Robert Siliciano at Johns Hopkins University in Baltimore, along with colleagues from Yale University in New Haven, CT, Sun Yat-sen and Guangzhou Medical Universities in China, National Taiwan University Hospital in Taipei, North Carolina State University in Raleigh, and Washington University in St. Louis.

Shan and colleagues note that in untreated patients, HIV replicates continuously, avoiding immune responses through rapid evolution in a process known as viral escape. But then why should HIV bother to establish reservoirs, given this ability to evolve and evade? Based on their data, the researchers argue that latency is simply an “unfortunate consequence” of CD4+ T cell infection within a narrow time frame after T cells are activated.

They report that during the natural process of T cell transition from one functional state to another—referred to as EMT, or effector-to-memory transition—T cells temporarily increase the expression of CCR5, a critical receptor for HIV, and decrease the function of certain normal cell genes necessary for HIV growth. So the virus gets into the cells more easily via the abundant CCR5, but then is rendered dormant because of dampened gene activity.

Shan and associates didn’t stop there. They found that this process of viral latency could be interrupted by HIV-specific CD8+ killer T cells and concluded that their finding has “implications for elimination of latent HIV-1 infection by T cell-based vaccines.”

Dr. Laurence is amfAR’s senior scientific consultant.