HIV viral protein R induces loss of DCT1-type renal tubules

Khun Zaw Latt, Kidney Disease Section, Kidney Diseases Branch, NIDDK, NIH, Bethesda MD.
Teruhiko Yoshida, Kidney Disease Section, Kidney Diseases Branch, NIDDK, NIH, Bethesda MD.
Shashi Shrivastav, Kidney Disease Section, Kidney Diseases Branch, NIDDK, NIH, Bethesda MD.
Amin Abedini, Department of Medicine, Renal Electrolyte and Hypertension Division; Institute for Diabetes, Obesity, and Metabolism; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Jeff M. Reece, Advanced Light Microscopy & Image Analysis Core (ALMIAC), NIDDK, NIH, Bethesda, MD.
Zeguo Sun, Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
Hewang Lee, Departments of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC.
Koji Okamoto, Kidney Disease Section, Kidney Diseases Branch, NIDDK, NIH, Bethesda MD.
Pradeep Dagur, Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Jurgen Heymann, Kidney Disease Section, Kidney Diseases Branch, NIDDK, NIH, Bethesda MD.
Yongmei Zhao, Advanced Biomedical and Computational Sciences, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., NCI, Frederick, MD.
Joon-Yong Chung, Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD.
Stephen Hewitt, Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD.
Pedro A. Jose, Departments of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC.
Kyung Lee, Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
John Cijiang He, Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
Cheryl A. Winkler, Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute and Basic Research Program, Frederick National Laboratory for Cancer Research, Frederick, MD.
Mark A. Knepper, Epithelial Systems Biology Laboratory, Systems Biology Center, Division of Intramural Research, NHLBI, NIH, Bethesda, MD.
Tomoshige Kino, Laboratory for Molecular and Genomic Endocrinology, Division of Translational Medicine, Sidra Medicine, Doha, Qatar.
Avi Z. Rosenberg, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
Katalin Susztak, Department of Medicine, Renal Electrolyte and Hypertension Division; Institute for Diabetes, Obesity, and Metabolism; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Jeffrey B. Kopp, Kidney Disease Section, Kidney Diseases Branch, NIDDK, NIH, Bethesda MD.

Document Type

Journal Article

Publication Date

11-13-2023

Journal

bioRxiv : the preprint server for biology

DOI

10.1101/2023.02.02.526686

Keywords

HIV-related salt wasting; Viral protein R; distal convoluted tubule; single-nucleus RNA sequencing

Abstract

Hyponatremia and salt wasting is a common occurance in patients with HIV/AIDS, however, the understanding of its contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the expression level of the gene, encoding the Na-Cl cotransporter, which is responsible for sodium reabsorption in distal nephron segments, we performed single-nucleus RNA sequencing of kidney cortices from three wild-type (WT) and three Vpr-transgenic (Vpr Tg) mice. The results showed that the percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05), and that in Vpr Tg mice, expression was not different in DCT cell cluster. The DCT1 subcluster had fewer cells in Vpr Tg mice compared with WT (P < 0.01). Immunohistochemistry demonstrated fewer DCT1 segments in Vpr Tg mice. Differential gene expression analysis comparing Vpr Tg and WT in the DCT cluster showed , an inhibitor of apoptosis, to be the most downregulated gene. These observations demonstrate that the salt-wasting effect of Vpr in Vpr Tg mice is mediated by loss of DCT1 segments via apoptosis dysregulation.

Department

Medicine

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