Format

Send to

Choose Destination
Atherosclerosis. 2016 Jan;244:22-8. doi: 10.1016/j.atherosclerosis.2015.10.103. Epub 2015 Oct 30.

Lipid metabolism in patients infected with Nef-deficient HIV-1 strain.

Author information

1
Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, VIC, 3004, Australia.
2
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, 3010, Australia.
3
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.
4
Macfarlane Burnett Institute for Medical Research and Public Health, 85 Commercial Rd, Melbourne, VIC, 3004, Australia.
5
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.
6
Department of Microbiology, Immunology and Tropical Medicine, George Washington University, 2300 I St. NW, Ross Hall, Washington DC, 20037, USA.
7
Baker IDI Heart and Diabetes Institute, PO Box 6492, Melbourne, VIC, 3004, Australia. Electronic address: Dmitri.Sviridov@Bakeridi.edu.au.

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.

CONCLUSION:

Our findings are consistent with HIV protein Nef playing a significant role in pathogenesis of lipid-related metabolic complications of HIV disease.

KEYWORDS:

Dyslipidemias; HDL metabolism; HIV; Lipids; Lipoproteins; MicroRNA; Nef

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center