In partial fulfillment of the requirements for the degree of

Master of Science in Biology

in the

School of Biological Sciences

Qi An

Will defend her thesis

“THE EVOLUTIONARY BENEFITS OF LATENCY IN WITHIN-HOST HIV INFECTION DYNAMICS”

Wednesday, April 17, 2019

12:00 PM

Howie Physics N210

Thesis Advisor:

Dr. Joshua S. Weitz

School of Physics, School of Biological Sciences

Georgia Institute of Technology

Committee Members:

Dr. Samuel P. Brown

School of Biological Sciences

Georgia Institute of Technology

Dr. Daniel Coombs

Department of Mathematics

University of British Columbia

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. Actively 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 innovation 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.