Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells

Payne, Emily H.; Ramalingam, Dhivya; Fox, Donald T.; Klotman, Mary E.

doi:10.1128/jvi.01718-17

Cited by 16 publications

(4 citation statements)

References 140 publications

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“…Interestingly we observed four cellular fates for HIV-1 infected RTE cells: hypertrophy, cell death, proliferation and transcriptional silencing, consistent with viral latency. We have previously reported the presence of hypertrophic tubule cells in the Tg26 mouse model of renal infection and in HIVAN human biopsies, and demonstrated that this phenotype, together with cell cycle arrest and polyploidy are primarily induced by the expression of HIV-1 Vpr and its ability to impair cytokinesis [40][41][42]. The recapitulation of all those phenotypes in the in vitro model described here demonstrates that HIV-1 gene expression is responsible for the phenotypic changes observed in renal biopsies from HIV-1 infected individuals that correlated with renal dysfunction [5].…”

Section: Discussionmentioning

confidence: 99%

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

Hughes

Aktürk

Gnjatic

et al. 2020

Aids

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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.

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Section: Discussionmentioning

confidence: 99%

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

Hughes

Aktürk

Gnjatic

et al. 2020

Aids

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“…Comparably, at the suborganismal level, tissue stresses such as acute wounding or viral infection can induce polyploidy at the cellular level [6,7,[20][21][22][23], which can result in an increase in tissue mass via enlarged cells. This WGD response represents an alternative to generating new cells through cell division.…”

Section: Polyploidy As a Response To Acute Stressmentioning

confidence: 99%

Polyploidy: A Biological Force From Cells to Ecosystems

Fox

Soltis

et al. 2020

Trends in Cell Biology

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158

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Polyploidy, resulting from the duplication of the entire genome of an organism or cell, greatly affects genes and genomes, cells and tissues, organisms, and even entire ecosystems. Despite the wide-reaching importance of polyploidy, communication across disciplinary boundaries to identify common themes at different scales has been almost nonexistent. However, a critical need remains to understand commonalities that derive from shared polyploid cellular processes across organismal diversity, levels of biological organization, and fields of inquiryfrom biodiversity and biocomplexity to medicine and agriculture. Here, we review the current understanding of polyploidy at the organismal and suborganismal levels, identify shared research themes and elements, and propose new directions to integrate research on polyploidy toward confronting interdisciplinary grand challenges of the 21 st century. Polyploidy: A Common Biological Phenomenon Lacking Cross-Disciplinary StudyPolyploidy [whole-genome duplication (WGD); see Glossary], defined as having three or more sets of chromosomes, influences organisms in all clades of eukaryotic life and all levels of biological organization, from genes to cells to entire ecosystems (Figure 1). The intersection of these axes of biodiversity and biological scale offers new opportunity for insight and research innovation. Yet, polyploidy remains underexplored in many contexts, and its roles and impact in biological processes and across phylogeny are unclear. This lack of clarity derives, in part, from very limited communication across disciplinary boundaries to identify common themes at different scales. The genomics era has accelerated research on polyploidy and provided a shared platform for dialogue and potential interdisciplinary synergy. We argue that cross-disciplinary approaches are crucial to identifying common functions and regulation of polyploidy. HighlightsCommunication across disciplinary boundaries to identify common themes of polyploidy has been extremely limited.

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“…hypertrophy, cell death, proliferation and transcriptional silencing, consistent with viral latency. We have previously reported the presence of hypertrophic tubule cells in the Tg26 mouse model of renal infection and in HIVAN human biopsies, and demonstrated that this phenotype, together with cell cycle arrest and polyploidy are primarily induced by the expression of HIV-1 Vpr and its ability to impair cytokinesis [40][41][42]. The recapitulation of all those phenotypes in the in vitro model described here demonstrates that HIV-1 gene expression is responsible for the phenotypic changes observed in renal biopsies from HIV-1 infected individuals that correlated with renal dysfunction [5].…”

Section: Discussionmentioning

confidence: 99%

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

Hughes

Aktürk

Gnjatic

et al. 2020

Preprint

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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.

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Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells

Cited by 16 publications

References 140 publications

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

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

Polyploidy: A Biological Force From Cells to Ecosystems

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

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