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

Authors

• 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.

APA Citation

Latt, Khun Zaw; Yoshida, Teruhiko; Shrivastav, Shashi; Abedini, Amin; Reece, Jeff M.; Sun, Zeguo; Lee, Hewang; Okamoto, Koji; Dagur, Pradeep; Heymann, Jurgen; Zhao, Yongmei; Chung, Joon-Yong; Hewitt, Stephen; Jose, Pedro A.; Lee, Kyung; He, John Cijiang; Winkler, Cheryl A.; Knepper, Mark A.; Kino, Tomoshige; Rosenberg, Avi Z.; Susztak, Katalin; and Kopp, Jeffrey B., "HIV viral protein R induces loss of DCT1-type renal tubules" (2023). GW Authored Works. Paper 3816.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3816

Department

Medicine