Dynamics of HIV-1 Infection and Therapy In Vivo

Author

Joshua Abraham Horwitz

Date of Award

2016

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Nussenzweig Laboratory

Abstract

Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immune deficiency syndrome (AIDS), a disease responsible for extensive morbidity and mortality worldwide. Despite more than thirty years of research since the discovery of HIV-1, no cure or vaccine yet exists. HIV-1 infection, while treatable with suppressive antiretroviral therapy drugs (ART), establishes lifelong persistence in the infected host as a natural consequence of the viral life cycle and the dynamic properties of the human immune cells in which HIV-1 propagates. This persistence is driven by populations of rare, long-lived HIV-1-infected cells, termed latently infected cells (LICs), that are refractory to immune clearance and viral cytopathic effects. Interruption of suppressive therapy – even after years of continuous and effective treatment – rapidly leads to virological rebound, requiring infected persons to remain on ART indefinitely. As the need to maintain lifelong daily ART imposes a substantial compliance burden on those infected, two major goals of HIV-1 research, broadly, concern (1) developing new therapeutic modalities that may alleviate some drawbacks to ART, and (2) identifying means with which to target and eradicate LICs as an approach to curing HIV-1 infection. To these ends, in the first three chapters of my thesis, I discuss my work demonstrating the utility of highly potent anti-HIV-1 antibodies in a number of therapeutic contexts. As antibody therapy expectedly did not result in cure, I was later motivated to study the nature of LIC formation and persistence. The fourth chapter of this thesis outlines my work to develop new molecular tools to interrogate LICs in a humanized mouse model of HIV-1 infection.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

Recommended Citation

Horwitz, Joshua Abraham, "Dynamics of HIV-1 Infection and Therapy In Vivo" (2016). Student Theses and Dissertations. 300.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/300