Human immunodeficiency virus (HIV) targets and depletes CD4+ T cells, compromising the body's ability to fight off infections. Progressed HIV disease can lead to impaired renal function known as HIV-associated nephropathy (HIVAN). Epithelial cells are typically ineffective targets of HIV-1 as they lack the CD4 and CCR5 molecules that are involved in viral entry into CD4+ T cells. However, previous research in the laboratory of Dr. Benjamin K. Chen demonstrated that renal tubule epithelial (RTE) cells were capable of viral uptake through a T cell-mediated, but CD4-independent mechanism. In addition, experiments implicated heparan sulfate proteoglycans (HSPG) as possible attachment receptors for HIV-1 through their heparan sulfate (HS) polysaccharide chains. The addition of anti-HSPG and anti-syndecan 1 antibodies blocked virus transfer by approximately 50%, suggesting a role for HSPG in viral entry. As a result, the syndecan (SDC) class of heparan sulfate receptors were assessed for their potential to serve as attachment receptors for HIV-1 through knockout studies. A co-culture system with donor HIV-expressing Jurkat T cells and target renal tubular epithelial (HK2) cells were used as a system for HIVAN pathogenesis and enabled cell-to-cell viral transfer. Despite the generation of stable SDC gene knockout lines, no change in viral transfer was observed, suggesting redundant or alternate pathways for HIV-1 entry. Understanding viral entry into epithelial cells is crucial as these sites can serve as reservoirs for HIV-1, where it can continue to replicate even when plasma viral load has been sufficiently reduced with antiretroviral treatment.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/36299 |
| Date | 11 June 2019 |
| Creators | Ali, Naushin S. |
| Contributors | Symes, Karen, Chen, Benjamin K. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
Page generated in 0.0022 seconds