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"Macrophages as Long-Term HIV Reservoirs"

by
Paul Castellano
Cell Biology, Neuroscience, and Physiology Program
B.A. 2000, Kean University, Union, NJ
M.S, 2012, Montclair State University, Montclair, NJ


Thesis Advisor: Eliseo Eugenin, Ph.D.
Associate Professor, Department of Microbiology, Biochemistry, and Molecular Genetics

Wednesday, May 3, 2017
10:30 A.M., ICPH Auditorium


Abstract

According to the world Health Organization there are 35 million individuals infected with the human immunodeficiency virus (HIV) throughout the world, with a yearly death toll of 1.5 million. The advent of antiretroviral therapies (ART) has allowed infected individuals to live longer lives, but ART is not a cure. HIV persists and re-emerges after cessation of therapy, indicating long-term viral reservoirs maintain infection and are capable of re-establishing plasma viral load. The cellular sources and mechanisms of viral persistence are not completely understood, partially due to poor resolution when attempting to detect infected cells. In this work, we designed and tested a novel method to detect HIV reservoirs at the single-cell level by microscopy. Using this technique, we and others identified that macrophages containing integrated HIV DNA are present in biopsies of infected individuals on long-term ART. We further identify a signature metabolic shift in HIV infected macrophages that may be exploited as a target for pharmaceutical intervention and elimination of these infected cells. We also assess the effects of methamphetamine abuse on gap junctional communication and hemichannel opening in neurons and astrocytes, and identified that HIV and methamphetamine comorbidity synergistically increases cell death. Gap junction blockers can be used to reduce the synergistic apoptosis. Therefore, we developed a mechanism to alleviate those suffering from HIV and methamphetamine comorbidity, improved the resolution in HIV reservoir detection, and identified a metabolic shift during infection that may be exploited for pharmaceutical intervention.


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