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Manipulating the Immune Response to Fight HIV

We study virus-host interactions at the tissue levels leveraging non-human primates and ex vivo human tissue models to develop novel antiviral therapies, innovative prevention strategies with the ultimate goal to - one day - cure HIV.

Research Projects

Turning off HIV White Noise: Targeting TGF-β to Reverse HIV Latency and Enhance Immune Responses

HIV persists in all treated individuals, and viral rebound occurs when antiretroviral treatment is interrupted. Long-lived memory CD4+ T cells represent one of the most important cellular reservoirs for HIV. We hypothesize that the same mechanisms responsible for maintaining a pool of memory cells in a long-lived resting state during chronic infection are responsible for maintaining HIV in a latent state during ART. The 10,000-foot view is that cellular program/s that maintain immune T cells in a long-lived “resting” state and are responsible to avoid excessive cellular activation/proliferation in response to stimuli (antigen or inflammation) also inhibit HIV reactivation. The analogy that I like to make is that they act as “white noise” for HIV and immune cells increasing their activation threshold in a noisy environment. We started investigating this hypothesis by studying the impact of targeting TGF-b, the master regulator of mucosal immunity and one of the most potent endogenous immunosuppressive factors, on HIV latency. Levels of TGF-β remain elevated in HIV infected individuals even after years of fully suppressive therapy and contribute to the development of HIV comorbidities and premature aging. We hypothesize that blocking TGF-β will not only increase the frequency of latency reversal events, but also enhance the elimination of the viral reservoir by increasing its susceptibility to immune and viral-mediated cell death. We are testing this hypothesis using clinical stage TGF-β inhibitors in rhesus macaque models of HIV using cutting-hedge techniques such as immunoPET/CT with 64Cu-labelled anti-HIV/SIV probe, single cell and spatial transcriptomics.

We use anti-HIV envelope probes and immunoPET/CT to identify areas of viral replication. In this video, we show immunoPET/CT scans from an SIV infected, ARV-treated rhesus macaque before and after 3 cycles of TGF-β inhibitor.

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