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dc.contributor.advisorGanju, Ramesh
dc.contributor.advisorFisk, Harold
dc.contributor.advisorZhao, Helong
dc.creatorGregory, Cory
dc.description.abstractThe Leukocyte Specific Protein 1 (LSP1) gene encodes a filament-actin binding protein that affects leukocyte motility via cytoskeleton remodeling. In dendritic cells, current data shows that LSP1 interacts with DC-SIGN and causes enhanced virus transfer to T-cells, while not typically infecting dendritic cells. However, while its association in several HIV-related signaling pathways has been shown, its primary role during HIV pathogenesis in T-cells is unknown. To explore the potential role of LSP1 during HIV-1 infection in T-cells, LSP1 expression was altered in cell lines susceptible to cytopathic CXCR4-tropic HIV- 1 strains, which result in T-cell depletion characteristic of AIDS patients. Two different LSP1 mRNA binding sites were targeted for knockdown (KD) using an shRNA plasmid to transcriptionally silence LSP1 expression in MT4 cells, as well as a non-targeting shRNA control. The relative amount of free virus in the supernatant from infected cells was quantified by ELISA; LSP1-KD MT4 cells showed significant reduction in p24 levels by 3 days post-infection. This result was explored with an LTR-driven GHOST reporter to examine the relative levels of infectious vs. total virus produced. In this assay, LSP1-KD cells showed a significant reduction of infectious virion. An HIV-1 binding and entry assay showed significant reduction in binding in LSP1-KD cells, while the entry assay showed no difference. These findings suggest that LSP1 knockdown cells are less infectious due to inhibition between the egress and maturation stages of HIV replication. Interestingly, LSP1-KD cells showed lower levels of total HIV infection despite enhanced cell viability, meaning that less infection occurred despite there being more available cells to infect. Additionally, LSP1-KD reduces the infectiousness of HIV-1 virion produced. Therefore, understanding the physiology of LSP1 during HIV-1 pathogenesis could provide novel therapeutic strategies to protect against HIV-1 and enhance T-cell viability.en_US
dc.description.sponsorshipNational Institutes of Health (Through Dr. Ramesh Ganju's R01 Grants)en_US
dc.description.sponsorshipOSU Department of Pathologyen_US
dc.description.sponsorshipOSU Arts & Sciences Honors Programen_US
dc.publisherThe Ohio State Universityen_US
dc.relation.ispartofseriesThe Ohio State University. Department of Molecular Genetics Honors Theses; 2014en_US
dc.subjectLeukocyte Specific Proteinen_US
dc.subjectT Cellsen_US
dc.subjectHIV Pathogenesisen_US
dc.titleThe Role of Leukocyte Specific Protein 1 (LSP1) during HIV-1 Infection in Human T Cellsen_US
dc.description.embargoNo embargoen_US
dc.description.academicmajorAcademic Major: Molecular Geneticsen_US
dc.description.academicmajorAcademic Major: Psychologyen_US

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