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

•Patients infected with Nef-deficient strain of HIV(ΔNefHIV) have reduced prevalence of hypoalphalipoproteinema.•Several lipid classes in plasma lipidomic profile are different in patients infected with WT HIV and ΔNefHIV.•HIV induced changes in profile of lipid metabolism related microRNA are attenuated in ΔNefHIV patients.•Findings are consistent with Nef playing a significant role in lipid abnormalities in HIV patients.

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