The assays that have been applied to measure the latent reservoir in studies performed to date have been imprecise, in some cases non-specific, and in all cases near the threshold of detection for specimens obtained from subjects effectively treated with antiretroviral therapy. A successful Collaboratory effort to eradicate the latent reservoir must have assays available that can reliably quantify this reservoir and measure reductions in its size. In Project 4.1, superior assays in development for integrated viral DNA and for viral infectivity will be refined and validated for HIV, and then applied to both the SIV and RT-SHIV macaque models. They will then be applied to in vitro models of latency and to cells and tissues obtained from infected macaques and HIV-infected study subjects, as part of other Collaboratory research projects. Microfluidic applications to these assays will address the question of the representativeness of the proviral reservoir for replication-competent virus and try to explain some of the mechanisms for replication in competent virus. The presence of HIV DNA and infectivity in blood macrophages, as a potential reservoir, will also be examined. These studies to improve measurements of the latent reservoir and interventions to purge it will involve close interactions and the exchange of methods and materials with several of the project and core Collaboratory investigators.
Assays are inadequate to measure the latent reservoir and the effect of treatments to reduce it. This project with refine innovative new assays to address this problem and then apply them to projects in the Collaboratory. In addition with innovative microfluidic technology this project will address the relationship of HIV DNA integrated in host cells and infectious virus in this latent reservoir.
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|Martin, Alyssa R; Pollack, Ross A; Capoferri, Adam et al. (2017) Rapamycin-mediated mTOR inhibition uncouples HIV-1 latency reversal from cytokine-associated toxicity. J Clin Invest 127:651-656|
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|Boehm, Daniela; Ott, Melanie (2017) Flow Cytometric Analysis of HIV-1 Transcriptional Activity in Response to shRNA Knockdown in A2 and A72 J-Lat Cell Lines. Bio Protoc 7:|
|Chaillon, Antoine; Nakazawa, Masato; Wertheim, Joel O et al. (2017) No Substantial Evidence for Sexual Transmission of Minority HIV Drug Resistance Mutations in Men Who Have Sex with Men. J Virol 91:|
|Sung, Julia A; Sholtis, Katherine; Kirchherr, Jennifer et al. (2017) Vorinostat Renders the Replication-Competent Latent Reservoir of Human Immunodeficiency Virus (HIV) Vulnerable to Clearance by CD8 T Cells. EBioMedicine 23:52-58|
|Akrami, Kevan; Coletta, Joelle; Mehta, Sanjay et al. (2017) Gordonia sternal wound infection treated with ceftaroline: case report and literature review. JMM Case Rep 4:e005113|
|Gianella, Sara; Taylor, Jeff; Brown, Timothy R et al. (2017) Can research at the end of life be a useful tool to advance HIV cure? AIDS 31:1-4|
|Bosque, Alberto; Nilson, Kyle A; Macedo, Amanda B et al. (2017) Benzotriazoles Reactivate Latent HIV-1 through Inactivation of STAT5 SUMOylation. Cell Rep 18:1324-1334|
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