PT  - JOURNAL ARTICLE
AU  - Kelly Hughes
AU  - Guray Akturk
AU  - Sacha Gnjatic
AU  - Benjamin Chen
AU  - Mary Klotman
AU  - Maria Blasi
TI  - Proliferation of HIV-infected renal epithelial cells following virus acquisition from infected macrophages
AID  - 10.1101/2020.03.27.011916
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.27.011916
4099  - http://biorxiv.org/content/early/2020/03/29/2020.03.27.011916.short
4100  - http://biorxiv.org/content/early/2020/03/29/2020.03.27.011916.full
AB  - Objectives HIV-1 can infect and persist in different organs and tissues, resulting in the generation of multiple viral compartments and reservoirs. Increasing evidence supports the kidney as such a reservoir. Previous work demonstrated that HIV-1 infected CD4+ T-cells transfer virus to renal tubule epithelial (RTE) cells 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.Design and Methods Multiparametric histochemistry analysis was performed on kidney biopsies from individuals with HIV-1 associated nephropathy (HIVAN). Primary monocyte-derived macrophages were infected with a (GFP)-expressing replication competent HIV-1. HIV-1 transfer from macrophages to RTE cells was carried out in a co-culture system and evaluated by fluorescence-microscopy and flow-cytometry. Live imaging was performed to assess the fate of HIV-1 infected RTE cells over time.Results We show that macrophages are abundantly present in the renal inflammatory infiltrate of individuals with HIVAN. 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.Conclusions Our study suggests that macrophages may play a 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.