title: Renal HIV expression is unaffected by serum LPS levels in an HIV transgenic mouse model of LPS induced kidney injury.
abstract: Acute kidney injury (AKI) is associated with increased rates of mortality. For unknown reasons, HIV infected individuals have a higher risk of AKI than uninfected persons. We tested our hypothesis that increased circulating LPS increases renal expression of HIV and that HIV transgenic (Tg26) mice have increased susceptibility to AKI. Tg26 mice harbor an HIV transgene encoding all HIV genes except gag and pol, and develop a phenotype analogous to HIVAN. Mice were used at 4-6 weeks of age before the onset of gross renal disease. Mice were injected i.p. with LPS or sterile saline. Renal function, tubular injury, cytokine expression, and HIV transcription were evaluated in Tg26 and wild type (WT) mice. LPS injection induced a median 60.1-fold increase in HIV expression in spleen but no change in kidney. There was no significant difference in renal function, cytokine expression, or tubular injury scores at baseline or 24 hours after LPS injection. HIV transcription was also analyzed in vitro using a human renal tubular epithelial cell (RTEC) line. HIV transcription increased minimally in human RTEC, by 1.47 fold, 48 hours after LPS exposure. We conclude that Tg26 mice do not increase HIV expression or have increased susceptibility to LPS induced AKI. The increased risk of AKI in HIV infected patients is not mediated via increased renal expression of HIV in the setting of sepsis. Moreover, renal regulation of HIV transcription is different to that in the spleen.
authors.affiliation: Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York City, New York, United States of America. jeremy.leventhal@mssm.edu
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Leventhal
authors.forename: Zygimantas
authors.initials: Z
authors.lastname: Alsauskas
authors.forename: Alexandra
authors.initials: A
authors.lastname: Snyder
authors.forename: Pengfei
authors.initials: P
authors.lastname: Gong
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Vivette
authors.initials: V
authors.lastname: D'Agati
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ross
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004195:Disease Models, Animal; D006678:HIV / Q000235:genetics / Q000302:isolation & purification*; D007668:Kidney / Q000821:virology*; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000821:virology; D008070:Lipopolysaccharides / Q000097:blood*; D051379:Mice; D008822:Mice, Transgenic; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D008070:Lipopolysaccharides