title: Lipid metabolism in patients infected with Nef-deficient HIV-1 strain.
abstract: BACKGROUND
  HIV protein Nef plays a key role in impairing cholesterol metabolism in both HIV infected and bystander cells. The existence of a small cohort of patients infected with Nef-deficient strain of HIV presented a unique opportunity to test the effect of Nef on lipid metabolism in a clinical setting.
  
  
  METHODS
  Here we report the results of a study comparing six patients infected with Nef-deficient strain of HIV (ΔNefHIV) with six treatment-naïve patients infected with wild-type HIV (WT HIV). Lipoprotein profile, size and functionality of high density lipoprotein (HDL) particles as well as lipidomic and microRNA profiles of patient plasma were analyzed.
  
  
  RESULTS
  We found that patients infected with ΔNefHIV had lower proportion of subjects with plasma HDL-C levels <1 mmol/l compared to patients infected with WT HIV. Furthermore, compared to a reference group of HIV-negative subjects, there was higher abundance of smaller under-lipidated HDL particles in plasma of patients infected with WT HIV, but not in those infected with ΔNefHIV. Lipidomic analysis of plasma revealed differences in abundance of phosphatidylserine and sphingolipids between patients infected with ΔNefHIV and WT HIV. MicroRNA profiling revealed that plasma abundance of 24 miRNAs, many of those involved in regulation of lipid metabolism, was differentially regulated by WT HIV and ΔNefHIV.
  
  
  CONCLUSIONS
  Our findings are consistent with HIV protein Nef playing a significant role in pathogenesis of lipid-related metabolic complications of HIV disease.
authors.affiliation: Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, VIC, 3004, Australia.
authors.forename: Hann
authors.initials: H
authors.lastname: Low
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: Lesley
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, VIC, 3004, Australia; Institut de Resercha Biomedica Bellvitge, University of Barcelona, Gran Via de l'Hospitalet, 199, 08908 Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Maria-Silvana
authors.initials: MS
authors.lastname: Di Yacovo
authors.affiliation: Macfarlane Burnett Institute for Medical Research and Public Health, 85 Commercial Rd, Melbourne, VIC, 3004, Australia.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Churchill
authors.affiliation: Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, VIC, 3004, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Meikle
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, George Washington University, 2300 I St. NW, Ross Hall, Washington DC, 20037, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bukrinsky
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Hill
authors.affiliation: Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, VIC, 3004, Australia. Electronic address: Dmitri.Sviridov@Bakeridi.edu.au.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Sviridov
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000172:deficiency*
chemical_list: D008055:Lipids; D012367:RNA, Viral; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1
keywords: Dyslipidemias; HDL metabolism; HIV; Lipids; Lipoproteins; MicroRNA; Nef