Directory Calendar News Careers Alumni Giving

IDM Dissertation Defenses

IDM Dissertations

Upcoming Dissertation Defenses



No events to display

Recent Dissertations

IDM Dissertation Defense

Diana Campbell Delucia - PhD '18: Cellular cholesterol regulation of HIV-1 trafficking during...

Thursday 3/1 11:00AM - 1:00PM
Public Health Lecture Hall (A115)

CELLULAR CHOLESTEROL REGULATION OF HIV-1 TRAFFICKING DURING MACROPHAGE-MEDIATED TRANS INFECTION

Abstract: Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4+ T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism. When comparing healthy HIV-1 seronegatives (SN), rapid progressors (PR), and NP, we found that monocyte-derived MΦ from NP did not mediate HIV-1 trans infection of autologous CD4+ T cells, in contrast to efficient trans infection mediated by SN and PR MΦ. MΦ trans infection efficiency was directly associated with the number of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)-expressing MΦ. Significantly fewer NP MΦ expressed DC-SIGN. Unesterified (free) cholesterol in MΦ cell membranes was significantly lower in NP than PR, as well as virus internalization in early endosomes. Furthermore, simvastatin (SIMV), decreased the subpopulation of DC-SIGN+ MΦ, as well as MΦ cis and trans infection. Notably, SIMV decreased cell membrane cholesterol and led to lipid raft dissociation, effectively mimicking the incompetent APC trans infection environment characteristic of NP. Our data support that DC-SIGN and membrane cholesterol are central to MΦ trans infection, and a lack of these limits HIV-1 disease progression. Lastly, we identified differentially expressed miRNA in NP and PR plasma which may contribute to the altered cholesterol phenotype we have identified in NP APC. Understanding the mechanisms of HIV-1 trans infection has great public health importance. For example, targeting the ability of MΦ to drive HIV-1 dissemination in trans could significantly enhance HIV-1 therapeutic strategies.

Advisor: Giovanna Rappocciolo

Last Updated On Friday, March 30, 2018 by Abby Kincaid
Created On Monday, February 26, 2018

Questions and Submissions

The schedule of defenses in the Department of Infectious Diseases and Microbiology is maintained by:

Abby Kincaid
abm82@pitt.edu 
412-624-3331

Share the details for your defense to ensure it is displayed here as well as on the department calendar, Pitt Public Health's calendar, Weekly Update, and LCD screens.

© 2018 by University of Pittsburgh Graduate School of Public Health

Login  |  Sitemap