Enhancement of Hiv Persistence By Adipose Tissue

<p>A major challenge for HIV eradication is the persistence of cellular and anatomic viral reservoirs. The primary cellular reservoirs for HIV, memory CD4 T cells and macrophages, traffic into various tissues where most viral replication occurs, or in the case of virally-suppressed antiretroviral-treated patients, the virus becomes dormant and protected from drugs and immune responses. The major tissue reservoirs for HIV include lymphoid tissues such as lymph nodes, bone marrow, and gastrointestinal lymphoid tissues, but adipose tissues could potentially harbor HIV as well. Adipose tissues are ubiquitous connective tissues and major sites of infiltration and immune activity by T cells and macrophages. As adipose tissue regulates CD4 T cell migration and functions, we hypothesized that adipocytes may affect HIV replication and serve as a reservoir for infected immune cells. To study the role of adipocytes for HIV infection, HIV-infected memory CD4 T cells were cocultured with primary adipocytes in vitro to determine if adipocytes influence HIV replication. Adipocytes alone did not affect HIV replication, but via IL6 and integrin ligands, did enhance T cell activation and HIV replication in cooperation with the ubiquitous common gamma-chain cytokines, IL2, IL7, or IL15. Adipocytes further enhanced T cell viability and even mitigated the viral suppressive effects of some antiretroviral drugs. To determine if adipose depots are sites for HIV persistence in vivo, adipose tissues of infected humans and rhesus macaques were examined for memory CD4 T cells and viral DNA. Within the stromal-vascular-fraction cellular component of adipose tissues (AT-SVF), activated memory CD4 T cells and provirus were readily detectable in all infected humans (n=5) and rhesus macaques (n=8) so far examined, and at frequencies comparable to other major viral tissue reservoirs. Thus, adipocytes have the capacity for promoting HIV replication, and adipose tissues of humans and monkeys appear to be sites of chronic immune activation and sanctuaries for HIV and SIV, which pose additional obstacles for viral eradication.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2015

Author dc:creator

• Couturier, Jacob

Contributors dc:contributor

• Dorothy E. Lewis, PhD
• Ashok Balasubramanyam, MD
• K. Jagannadha Sastry, PhD

• HIV replication
• CD4 T cells
• Adipose tissue
• Lipodystrophy
• Immunology of Infectious Disease

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/612

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1648