title: Short Communication: Accumulation of Neutral Lipids in Liver and Aorta of Nef-Transgenic Mice.
abstract: HIV-infected individuals are at high risk of developing atherosclerosis and cardiovascular disease, in part, due to HIV-induced impairment of cholesterol metabolism. In vitro studies demonstrated that HIV-1 protein Nef inhibits activity of ABCA1, the main cellular cholesterol transporter, leading to cholesterol accumulation in macrophages and conversion of these cells into foam cells, characteristic for atherosclerosis. However, the mechanisms of Nef-mediated effects on cholesterol metabolism in vivo are not well characterized. In this study, we generated Nef-transgenic mice and evaluated the accumulation of neutral lipids in liver and aorta of these animals. Nef expression was low in all transgenic mice, with some mice carrying the Nef transgene, but not expressing the Nef RNA. Using Oil Red O staining, we demonstrated increased levels of neutral lipids in liver and aorta of mice expressing Nef relative to transgenic animals, with no detectable Nef expression or control wild-type mice. These results provide direct evidence that Nef promotes cholesterol deposition in tissues.
authors.affiliation: 1 George Washington University School of Medicine and Health Sciences , Washington, District of Columbia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Pushkarsky
authors.affiliation: 2 Lomonosov Moscow State University , Moscow, Russia .
authors.forename: Evgeny
authors.initials: E
authors.lastname: Shilov
authors.affiliation: 2 Lomonosov Moscow State University , Moscow, Russia .
authors.forename: Natalya
authors.initials: N
authors.lastname: Kruglova
authors.affiliation: 3 Max-Planck Institute for Molecular Genetics , Dresden, Germany .
authors.forename: Ronald
authors.initials: R
authors.lastname: Naumann
authors.affiliation: 1 George Washington University School of Medicine and Health Sciences , Washington, District of Columbia.
authors.forename: Beda
authors.initials: B
authors.lastname: Brichacek
authors.affiliation: 1 George Washington University School of Medicine and Health Sciences , Washington, District of Columbia.
authors.forename: Lucas
authors.initials: L
authors.lastname: Jennelle
authors.affiliation: 4 Baker IDI Heart and Diabetes Institute , Melbourne, Victoria, Australia .
authors.forename: Dmitri
authors.initials: D
authors.lastname: Sviridov
authors.affiliation: 2 Lomonosov Moscow State University , Moscow, Russia .|5 Engelhardt Institute of Molecular Biology , Russian Academy of Sciences, Moscow, Russia .|6 German Rheumatism Research Center , Berlin, Germany .
authors.forename: Andrei
authors.initials: A
authors.lastname: Kruglov
authors.affiliation: 2 Lomonosov Moscow State University , Moscow, Russia .|5 Engelhardt Institute of Molecular Biology , Russian Academy of Sciences, Moscow, Russia .|6 German Rheumatism Research Center , Berlin, Germany .
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Nedospasov
authors.affiliation: 1 George Washington University School of Medicine and Health Sciences , Washington, District of Columbia.
authors.forename: Michael
authors.initials: M
authors.lastname: Bukrinsky
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D006651:Histocytochemistry; D008055:Lipids / Q000032:analysis*; D008099:Liver / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013194:Staining and Labeling; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008055:Lipids; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1
keywords: HIV-1; Nef; cholesterol efflux; lipid droplets