HIV-1 entry in renal tubule epithelial cells through HSPG-dependent uptake pathways


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

Similar works

Having an issue?

Is data on this page outdated, violates copyrights or anything else? Report the problem now and we will take corresponding actions after reviewing your request.