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Research
Labs: Linqi Zhang, Ph.D.
HIV-1 Pathogenesis Better understanding of the dynamics of HIV-1 replication in vivo has provided an important rationale for early and aggressive treatment of this infection. With combination antiretroviral therapy, it is now possible to suppress HIV-1 replication in infected individuals to an extent that the virus becomes undetectable in the plasma for over two years. For the first time in the history of this epidemic, eradication of HIV-1 from an infected person is a real scientific objective. However, a major obstacle to HIV-1 elimination became apparent when replication-competent virus was found to reside latently within resting memory CD4+ lymphocytes, since such cells are known to have a prolonged lifespan. In addition, this latent reservoir of HIV-1 was found to persist after a couple of years of seemingly effective combination antiretroviral therapy, even in patients whose treatment was initiated during the primary phase of infection. We therefore have focused on studying of residual viral replication, as well as for the decay of the latent reservoir, in patients who had been completely undetectable for ~2-3 years while on triple- or quadruple-drug combination therapy. Virologic and immunologic characterization of these patients has provided significant insights into the pathogenesis of HIV-1 infection. The thymus plays a crucial role in the development of T lymphocytes during ontogeny and is believed to have a significant impact on T lymphocyte regeneration in adulthood. It is generally believed that there is an age-related reduction in thymic regenerative capacity in normal individuals. Multiple lines of evidence indicate that thymocytes are infectable by HIV and SIV both in vitro and in vivo. Autopsy studies of HIV-1-infected humans or SIV-infected macaques show both infection and altered histopathology of the thymus. To better understand the role of the thymus in HIV/SIV infection we are studying critical factors in the understanding of HIV/SIV pathogenesis and the capacity for immune reconstitution. Genotypic and Phenotypic Diversity of HIV HIV-1 exists as a divergent swarm of viral quasi-species both in infected individuals and in different geographic locations. The complexity in diversity has posed tremendous difficulties for the human immune system while being of enormous benefit to the virus. We seek to better understand the mechanisms and consequences of this diversity in order to facilitate the future design and development of therapeutic and vaccine approaches. Generation of replication-competent single-cycle simian immunodeficiency virus (SIV) for potential vaccine studies Development of an effective anti-HIV vaccine is of vital importance to prevent HIV infection and to reduce the spread of AIDS. Although a number of vaccines have been developed, the majority carry intrinsic properties which render these vaccines either ineffective or potentially risky. The primary goal of our effect is to develop an effective anti-HIV vaccine by exploring a completely novel strategy. The unique characteristics of the novel strategy allows the viral infection to undergo only a single cycle, thereby preventing the potential risks associated with inactivated whole virus vaccine and live attenuated virus vaccine, and at the same time, preserving the conformational integrity of infecting viral particles that are important to generate a strong and protective immune response.
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The
role of the thymus in HIV/SIV infection before and after treatment
with combination therapy
