Abstract
The final obstacle to achieving a cure to HIV/AIDS is the presence of latent HIV reservoirs scattered throughout the body. Although antiretroviral therapy maintains plasma viral loads below the levels of detection, upon cessation of therapy, the latent reservoir immediately produces infectious progeny viruses. This results in elevated plasma viremia, which leads to clinical progression to AIDS. Thus, if a HIV cure is ever to become a reality, it will be necessary to target and eliminate the latent reservoir. To this end, tremendous effort has been dedicated to locate the viral reservoir, understand the mechanisms contributing to latency, find optimal methods to reactivate HIV, and specifically kill latently infected cells. Although we have not yet identified a therapeutic approach to completely eliminate HIV from patients, these efforts have provided many technological breakthroughs in understanding the underlying mechanisms that regulate HIV latency and reactivation in vitro. In this review, we summarize and compare experimental systems which are frequently used to study HIV latency. While none of these models are a perfect proxy for the complex systems at work in HIV+ patients, each aim to replicate HIV latency in vitro.
Highlights
Antiretroviral therapy (ART) regimens keep the virus below the level of detection in HIV+individuals
Many studies on HIV latency and reactivation instead rely on tissue culture systems using immortalized human cell lines or primary cells derived from human blood or tissues [10,11]
We present several stable cell line and primary cell models used to study HIV latency in order to provide a comprehensive comparison of the different available systems
Summary
Antiretroviral therapy (ART) regimens keep the virus below the level of detection in HIV+. In HIV+ individuals, HIV-infected cells can be detected in the peripheral blood and lymph nodes, and in the brain, lungs, kidneys, liver, adipose tissues, gastrointestinal tract, genitourinary systems, and bone marrow Lymphoid tissues, such as spleen, thymus, and gut-associated lymphoid tissues (GALT), are the most important viral reservoirs, which remain relatively dormant, but account for the immediate rebounds in viremia following cessation of ART [1,3]. Many studies on HIV latency and reactivation instead rely on tissue culture systems using immortalized human cell lines or primary cells derived from human blood or tissues [10,11] These in vitro culture models utilize different combinations of growth factors, feeder cells, and cytokines to drive HIV-infected, activated T cells into a quiescent state, with the goal of modeling the conditions of latently infected T central or effector memory (Tcm or Tem) cells [12,13,14]. We present several stable cell line and primary cell models used to study HIV latency in order to provide a comprehensive comparison of the different available systems
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