HIV-1 genes vpr and nef synergistically damage podocytes, leading to glomerulosclerosis

Yiqin Zuo, Taiji Matsusaka, Jianyong Zhong, Ji Ma, Li Jun Ma, Zaher Hanna, Paul Jolicoeur, Agnes B. Fogo, Iekuni Ichikawa

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

This study aimed to identify the causative gene for HIV-1 associated nephropathy, a paradigmatic podocytopathy. A previous study demonstrated that transgenic expression of nonstructural HIV-1 genes selectively in podocytes in mice with FVB/N genetic background resulted in podocyte injury and glomerulosclerosis. In this study, transgenic mice that expressed individual HIV-1 genes in podocytes were generated. Five of six transgenic mice that expressed vpr developed podocyte damage and glomerulosclerosis. Analysis of an established vpr transgenic line revealed that transgenic mice on FVB/N but not on C57BL/6 genetic background developed podocyte injury by 8 wk of age, with later glomerulosclerosis. Four of 11 transgenic mice that expressed nef also developed podocyte injury. One transgenic line was established from the nef founder mouse with the mildest phenotype. Transgenic mice in this line developed mesangial expansion at 3 wk of age and mild focal podocyte damage at 10 wk of age. Mating with FVB/N mice did not augment nephropathy. None of the transgenic mice that expressed vif, tat, rev, or vpu in podocytes, even with the FVB/N genetic background, developed podocyte injury. For testing effects of simultaneous expression of vpr and nef, these two lines were mated. All nef:vpr double-transgenic mice showed severe podocyte injury and glomerulosclerosis by 4 wk of age. In contrast, all vpr or nef single-transgenic mice in the same litter uniformly showed no or much milder podocyte injury. These findings indicate that vpr and nef each can induce podocyte injury with a prominent synergistic interaction.

Original languageEnglish (US)
Pages (from-to)2832-2843
Number of pages12
JournalJournal of the American Society of Nephrology
Volume17
Issue number10
DOIs
StatePublished - Oct 2006
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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