Fates of HIV-infected Renal Epithelial Cells Following Virus Acquisition from Infected Macrophages

Abstract

Although anti-retroviral therapy (ART) is effective at controlling HIV-1 replication, it does not eradicate the virus from viral reservoirs established throughout the body of infected individuals before therapy initiation.

Increasing evidence supports the kidney as such a reservoir. Although it is recognized that HIV-1 infects renal tubule epithelial (RTE) cells, how the virus enters kidney cells and their fate following infection requires further investigation. Previous work has demonstrated that HIV-1 infected CD4+ T-cells transfer virus to RTE through cell-to-cell contact. In addition to CD4+ T-cells, macrophages represent the other major target of HIV-1. Renal macrophages induce and regulate inflammatory responses and are critical to homeostatic regulation of the kidney environment. Combined with their ability to harbor virus, macrophages may also play an important role in the spread of HIV-1 infection in the kidney.

Here we show that macrophages are abundantly present in the renal inflammatory infiltrate of individuals with HIV-associated nephropathy (HIVAN). Using a co-culture system, we observed contact-dependent HIV-1 transfer from infected macrophages to both primary and immortalized renal cells. Live imaging of HIV-1 infected RTE cells revealed four different fates: proliferation, hypertrophy, latency and cell death.

The work described here indicates that macrophages may play an important role in the dissemination of HIV-1 in the kidney and that proliferation of infected renal cells may contribute to HIV-1 persistence in this compartment. Additionally, the model presented here shows that renal cell infection results in pathological changes consistent with what is seen in vivo.

Description

Provenance

Citation

Citation

Hughes, Kelly T (2020). Fates of HIV-infected Renal Epithelial Cells Following Virus Acquisition from Infected Macrophages. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/21018.

Collections


Dukes student scholarship is made available to the public using a Creative Commons Attribution / Non-commercial / No derivative (CC-BY-NC-ND) license.