Understanding the role of dendritic cells during HIV transmission and latency expansion
| dc.contributor.author | Parvarchian, Roshan | |
| dc.contributor.examiningcommittee | Marshall, Aaron (Immunology) | en_US |
| dc.contributor.examiningcommittee | Fowke, Keith ( Medical Microbiology and Infectious Diseases) | en_US |
| dc.contributor.supervisor | Murooka, Thomas | |
| dc.date.accessioned | 2022-05-31T20:28:35Z | |
| dc.date.available | 2022-05-31T20:28:35Z | |
| dc.date.copyright | 2022-05-31 | |
| dc.date.issued | 2022-07-31 | |
| dc.date.submitted | 2022-05-31T19:38:11Z | en_US |
| dc.degree.discipline | Immunology | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | HIV dissemination from the genital mucosal tract to the lymphoid organs is the first critical step towards systemic infection. We and others have previously shown that upon sexual HIV exposure, a local pool of infected cells is found in the genital mucosae, followed by rapid HIV spread into the draining lymphoid tissues before detection in the blood. We extended these observations by addressing the role of DCs in the transfer of HIV particles to susceptible CD4+ T cells through trans-infection. Our laboratory previously showed that CD4+ T cells engaged in prolonged contacts with HIV-bearing DCs that was dependent on gp120:CD4 and LFA-1: ICAM-1 adhesive contacts. Abrogating stable DC: T cell contacts significantly reduced HIV transmission. However, a knowledge gap is a molecular mechanism that facilitates the efficient transfer of HIV through HIV+ DC: T cell contacts. Here, using a custom human kinomics array platform, I identified distinct signaling pathways that are activated in CD4+ T cells during in vitro co-culture with DCs bearing wildtype HIV, but not in HIVīEnv. Utilizing functional network analysis programs, such as IPA and InnateDB, I demonstrated that mTOR, ERK, and Ca2+ pathways are upregulated during DC: T cell contacts in the presence of wildtype, but not Env-deficient HIV. These data suggest that T cells accumulate signals downstream of the CD4 molecule that impacts their motility and function as they contact HIV-bearing DCs, some of which are prerequisite for efficient viral infection and ultimately systemic spread. | en_US |
| dc.description.note | October 2022 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/36511 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | HIV | en_US |
| dc.subject | Dendritic cells | en_US |
| dc.subject | T cells | en_US |
| dc.subject | Latency | en_US |
| dc.subject | T cell signaling pathway | en_US |
| dc.title | Understanding the role of dendritic cells during HIV transmission and latency expansion | en_US |
| dc.type | master thesis | en_US |