Proliferation of HIV-infected renal epithelial cells following virus acquisition from infected macrophages

Abstract

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+ Tcells 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 coculture 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.3 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.

Astrocytes are HIV reservoirs in the brain: A cell type with poor HIV infectivity and replication but efficient cell‐to‐cell viral transfer

“…Our studies in astrocytes also can be extended to a recent publication that characterizes infection of renal cells that are CD4 negative and can spread infection and damage into neighboring cells, including macrophages (Hughes et al., 2020). The role of the virological synapses and transfer into immune cells probably is similar to the mechanism described in astrocytes (Hughes et al., 2020).…”

“…Our studies in astrocytes also can be extended to a recent publication that characterizes infection of renal cells that are CD4 negative and can spread infection and damage into neighboring cells, including macrophages (Hughes et al., 2020). The role of the virological synapses and transfer into immune cells probably is similar to the mechanism described in astrocytes (Hughes et al., 2020). Thus, instead of proposing that astrocytes and renal tubular epithelial cells/macrophage axis are a rare HIV reservoirs; we propose that the development of new technologies to identify rare reservoirs will enable the discovery of new kinds of reservoirs.…”

Lactate drives cellular DNA repair capacity: Role of lactate and related short-chain fatty acids in cervical cancer chemoresistance and viral infection

“…In particular, such interactions that lead to activation or enhancement of the viral life cycle have been reported for adenoviruses (AV) (Baker et al, 2007;Nebenzahl-Sharon et al, 2019), adeno-associated viruses (AAV) (Choi et al, 2010), herpes simplex virus 1 (Muylaert and Elias, 2007;Smith et al, 2014;Edwards et al, 2018), VACV (Luteijn et al, 2018), John Cunningham virus (JC) (Darbinyan et al, 2004), and parvovirus B19 (Munakata et al, 2005), among others. Interestingly, the indispensable role of the NHEJ repair system in retroviral integration is widely accepted, though the role of DNA-PKcs in the HIV cycle is still disputable, especially in non-CD4 cells (Liu et al, 2013;Hughes et al, 2020;Wagner et al, 2021). The presence of viral proteins and their activity in host cells often contribute to altered activity of DSB repair pathways together with the attraction of particular DNA repair proteins to viral replication sites.…”