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

ABSTRACTObjectivesHIV-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 MethodsMultiparametric 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.ResultsWe 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.ConclusionsOur 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.

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Sensing of HIV-1 by TLR8 activates human T cells and reverses latency

Nature Communications ◽

10.1038/s41467-019-13837-4 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 8

Author(s):

Hany Zekaria Meås ◽

Markus Haug ◽

Marianne Sandvold Beckwith ◽

Claire Louet ◽

Liv Ryan ◽

...

Keyword(s):

T Cells ◽

Immune Cells ◽

Cd4 T Cells ◽

Vaccine Development ◽

Inflammatory Responses ◽

Cell Receptor ◽

Low Grade ◽

Activation Markers ◽

Adaptive Immune Cells ◽

Hiv 1

AbstractDuring HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood. Here we show that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17. In addition, we found that endosomal HIV induced cytokine secretion from CD4+ T cells in a TLR8-specific manner. TLR8 engagement also enhanced HIV-1 replication and potentiated the reversal of latency in patient-derived T cells. The adjuvant TLR8 activity in T cells can contribute to viral dissemination in the lymph node and low-grade inflammation in HIV patients. In addition, it can potentially be exploited for therapeutic targeting and vaccine development.

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HIV-1-Infected CD4+ T Cells Facilitate Latent Infection of Resting CD4+ T Cells through Cell-Cell Contact

Cell Reports ◽

10.1016/j.celrep.2018.07.079 ◽

2018 ◽

Vol 24 (8) ◽

pp. 2088-2100 ◽

Cited By ~ 20

Author(s):

Luis M. Agosto ◽

Melissa B. Herring ◽

Walther Mothes ◽

Andrew J. Henderson

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Latent Infection ◽

Cell Contact ◽

Hiv 1 ◽

Cell Cell

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Mode of Transmission Affects the Sensitivity of Human Immunodeficiency Virus Type 1 to Restriction by Rhesus TRIM5α

Journal of Virology ◽

10.1128/jvi.01046-08 ◽

2008 ◽

Vol 82 (22) ◽

pp. 11117-11128 ◽

Cited By ~ 55

Author(s):

Max W. Richardson ◽

Richard G. Carroll ◽

Matthew Stremlau ◽

Nikolay Korokhov ◽

Laurent M. Humeau ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Cd4 T Cells ◽

Hiv Transmission ◽

Human Cells ◽

Cell Contact ◽

Hiv Therapy ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Rhesus TRIM5α (rhTRIM5α), but not human TRIM5α (huTRIM5α), potently inhibits human immunodeficiency virus (HIV) infection and is thus a potentially valuable therapeutic tool. Primary human CD4 T cells engineered to express rhTRIM5α were highly resistant to cell-free HIV type 1 (HIV-1) infection. However, when cocultured with unmodified T cells, rhTRIM5α-expressing cells became highly permissive to HIV-1 infection. Physical separation of rhTRIM5α-expressing cells and unmodified cells revealed that rhTRIM5α efficiently restricts cell-free but not cell-associated HIV transmission. Furthermore, we observed that HIV-infected human cells could infect rhesus CD4 T cells by cell-to-cell contact, but the infection was self-limiting. Subsequently, we noted that a spreading infection ensued when HIV-1-infected rhTRIM5α-expressing human cells were cultured with huTRIM5α- but not rhTRIM5α-expressing cells. Our results suggest that cell-associated HIV transmission in humans is blocked only when both donor and recipient cells express rhTRIM5α. These studies further define the role of rhTRIM5α in cell-free and cell-associated HIV transmission and delineate the utility of rhTRIM5α in anti-HIV therapy.

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