{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T20:42:27Z","timestamp":1791751347521,"version":"4.3.4"},"reference-count":68,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":31,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01-DK115968"],"award-info":[{"award-number":["R01-DK115968"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01-DK098410"],"award-info":[{"award-number":["R01-DK098410"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01-DK120908"],"award-info":[{"award-number":["R01-DK120908"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01-DK103564"],"award-info":[{"award-number":["R01-DK103564"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017046","name":"School of Medicine, University of Maryland","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017046","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>People carrying two APOL1 risk alleles (RA) \u2013 G1 or G2 \u2013 are at greater risk of developing human immunodeficiency virus (HIV)-associated nephropathy (HIVAN). However, it remains unclear whether the encoded protein(s) (APOL1-RA) and HIV-1 Nef interact to induce podocyte cell death. Here, we generated transgenic flies that express APOL1-G1 (derived from a child with HIVAN) and HIV-1 nef specifically in the nephrocytes, the fly equivalent of mammalian podocytes, and assessed their individual and combined effects on the nephrocyte filtration structure and function. We found that HIV-1 Nef acts in synergy with APOL1-G1, resulting in nephrocyte structural and functional defects, and that Nef exacerbates the organelle acidification defects and autophagy reduction induced by APOL1-G1. The synergy between HIV-1 Nef and APOL1-G1 is built on their joint effects on elevating endoplasmic reticulum (ER) stress, triggering nephrocyte dysfunction and, ultimately, cell death. Thus, we identified ER stress as the converging point for the synergy between HIV-1 Nef and APOL1-G1 in inducing nephrocyte cell death. Given the high similarity between Drosophila nephrocytes and human podocytes, our findings suggest ER stress as a new therapeutic target for HIV-1- and APOL1-associated nephropathies.<\/jats:p>","DOI":"10.1242\/dmm.052178","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T10:03:11Z","timestamp":1754042591000},"source":"Crossref","is-referenced-by-count":1,"title":["HIV-1 Nef synergizes with APOL1-G1 to induce nephrocyte cell death in HIV-related kidney diseases"],"prefix":"10.1242","volume":"18","author":[{"given":"Jun-yi","family":"Zhu","sequence":"first","affiliation":[{"name":"Center for Precision Disease Modeling 1 , Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]},{"name":"University of Maryland School of Medicine 1 , Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]},{"name":"University of Maryland School of Medicine 2 Division of Endocrinology, Diabetes and Nutrition, Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Fu","sequence":"additional","affiliation":[{"name":"Center for Precision Disease Modeling 1 , Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]},{"name":"University of Maryland School of Medicine 1 , Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"van de Leemput","sequence":"additional","affiliation":[{"name":"Center for Precision Disease Modeling 1 , Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]},{"name":"University of Maryland School of Medicine 1 , Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]},{"name":"University of Maryland School of Medicine 2 Division of Endocrinology, Diabetes and Nutrition, Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[{"name":"Child Health Research Center 3 , Department of Pediatrics , , Charlottesville, VA 22903,","place":["USA"]},{"name":"University of Virginia School of Medicine 3 , Department of Pediatrics , , Charlottesville, VA 22903,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinliang","family":"Li","sequence":"additional","affiliation":[{"name":"Children's Research Institute, Children's National Health System 4 , Washington , DC 20012,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-9584","authenticated-orcid":false,"given":"Patricio E.","family":"Ray","sequence":"additional","affiliation":[{"name":"Child Health Research Center 3 , Department of Pediatrics , , Charlottesville, VA 22903,","place":["USA"]},{"name":"University of Virginia School of Medicine 3 , Department of Pediatrics , , Charlottesville, VA 22903,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5177-7798","authenticated-orcid":false,"given":"Zhe","family":"Han","sequence":"additional","affiliation":[{"name":"Center for Precision Disease Modeling 1 , Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]},{"name":"University of Maryland School of Medicine 1 , Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]},{"name":"University of Maryland School of Medicine 2 Division of Endocrinology, Diabetes and Nutrition, Department of Medicine , , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"2025080106030442700_DMM052178C1","doi-asserted-by":"publisher","first-page":"12537","DOI":"10.1128\/JVI.78.22.12537-12547.2004","article-title":"Murine T cells potently restrict human immunodeficiency virus infection","volume":"78","author":"Baumann","year":"2004","journal-title":"J. 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