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

Molecular characterization of HIV-1 Nef and ACOT8 interaction: insights from in silico structural predictions and in vitro functional assays

“…The Nef/ACOT8 association may also ensure an efficient HIV-1 virions budding, modifying the composition of membrane lipids. Interestingly, it has been reported that Nef plays a significant role in pathogenesis of lipid-related metabolic complications of HIV-1 infection 44 . However, whether Nef has any need to be localized to peroxisomes is not clear.…”

Immunometabolic and Lipidomic Markers Associated With the Frailty Index and Quality of Life in Aging HIV+ Men on Antiretroviral Therapy

“…HIV infection and antiretroviral therapy are both associated with significant disturbances in systemic metabolic regulation, including lipids, which play a central role in the host immune response, as previously reviewed ( Willig and Overton, 2016 ). While dyslipidemia is a recognized risk factor for age-related diseases, such as cardiovascular disease, only a handful of studies have investigated the plasma lipid profiles in HIV infection, and these have focused on cardiovascular risk prediction ( Wong et al, 2014 , Low et al, 2016 ). There is a paucity of data reflecting the association between dysregulated lipid metabolism with frailty.…”

Lipidomic dataset of plasma from patients infected with wild type and nef-deficient HIV-1 strain

“…They were compared with patients infected with Nef-positive (WT) HIV-1 strain ( n =6) and six HIV negative subjects selected from a group of healthy volunteers. Description of the patients is presented in the main paper [1] .…”

“…The data can be used to evaluate cardiovascular risk in HIV disease and to assess the role of nef in HIV-induced disturbances in systemic lipid metabolism. The full impact of nef deficiency on lipid and lipoprotein metabolism in HIV-infected patients is presented in the accompanying study “Lipid Metabolism in Patients Infected with Nef-deficient HIV-1 Strain” [1] .…”