Title:
Evolutionary benefits of latency in within-host HIV infection dynamics

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An, Qi
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Weitz, Joshua S.
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Abstract
HIV is a retrovirus that infects helper T cells (CD4 + T cells) in the human immune system. At the cellular scale, HIV generates both actively and latently infected cells. Ac- tively infected cells produce mature virions and are often the primary target of antiretroviral therapies. In contrast, latently infected T cells can do not produce virus particles, are hard to detect and treat, and can be reactivated to produce new virions. Understanding the dynamics of latent infections is critical to the development of strategies to treat and control the spread of HIV. In this thesis, we study a variant of within-host models of HIV infection dynamics including proliferation of both susceptible and latently infected CD4+ cells. In this model, HIV infection of susceptible cells can result in acute or latent infections. The key innova- tion here is to identify the relative contributions of the active and latent pathways towards viral fitness, both in the initial and later stages of the within-host dynamics. We do so by leveraging a new approach to decomposing viral fitness developed in the context of phage- bacteria interactions. Our work highlights how variation in susceptible cell densities, viral life history traits, and retroviral therapies jointly influence dynamic selection pressures for active and latent infections.
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2019-04-30
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