A humanized mouse model of HIV latency as a preclinical tooltowards functional HIV cure

Combined antiretroviral therapy (cART) has dramatically improved the clinical outcome of HIV-1 infected patients. Successful cART requires nevertheless lifetime adherence, has no effect on the eradication of viral reservoirs and does not restore an effective virus-suppressive immune response against HIV. Research on HIV pathogenesis and development of new therapeutic strategies have long been hampered by the lack of robust and reproducible preclinical models of HIV infection. In this regard, we have gained expertise in the generation and HIV infection of humanized NOD/LtszscidIL2null (NSG) strain to obtain a full human immune system. The objectives of the PhD project are: 1) to optimize an HIV latency model for the design of therapeutic vaccines and therapies targeting the long-lived reservoir of HIV infection using humanized NSG mice showing functional immune responses, 2) to determine whether innate immunity is a critical component of post-treatment control and containment of the viral reservoir using one immune-based therapeutic strategy in humanized mice, Ultimately, these investigations will provide important insights for the design of a therapeutic vaccine favoring the reduction of the residual HIV reservoir.