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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 (?NefHIV) 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 ?NefHIV 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 ?NefHIV. Lipidomic analysis of plasma revealed differences in abundance of phosphatidylserine and sphingolipids between patients infected with ?NefHIV 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 ?NefHIV. CONCLUSION:Our findings are consistent with HIV protein Nef playing a significant role in pathogenesis of lipid-related metabolic complications of HIV disease.

SUBMITTER: Low H

PROVIDER: S-EPMC4698210 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Low Hann H Cheng Lesley L Di Yacovo Maria-Silvana MS Churchill Melissa J MJ Meikle Peter P Bukrinsky Michael M Hill Andrew F AF Sviridov Dmitri D

Atherosclerosis 20151030

<h4>Background</h4>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.<h4>Methods</h4>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-typ ...[more]

PMID: 26581048

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Project description:Polymorphisms in some host genes have a significant impact on susceptibility to HIV-1 infection and rate of disease progression (1, 2). The purpose of the current sub-study was to find out the relationship between polymorphisms in genes involved in the lipid metabolism and the CD4/CD8 T-cell counts.Sub-study of a cross-sectional, observational study conducted in 468 patients with HIV infection attended at the outpatient clinic to investigate individual genetic predisposition to atherogenic dyslipidemia (AD). All patients were genetically characterized and all polymorphisms were in Hardy-Weinberg equilibrium. Thirteen polymorphisms were selected from nine genes: APOA5 (rs662799 and rs3135506); APOC3 (rs5128 and rs4520); LPL (rs328 and rs268); CETP (rs708272); HL (rs1800588); MTP (rs1800591); APOE (rs7412 and rs429358); LRP5 (rs7116604); and VLDLR (rs1454626). Lipid and lipoprotein parameters, CD4 and CD8 T-cell counts and plasma HIV-RNA were determinate. The statistical analysis was performed using SPSS statistical software version 19 (SPSS Inc., Chicago, IL, USA).We studied 468 HIV-infected patients (men, 77%), with a mean (SD) age of 45.9 (19.7) years. The mean CD4 T-cell count and nadir CD4 was 547 (459) and 193 (159) cells/µL, respectively; 78.7% of participants were virologically suppressed. Patients carrying rs3135506 in the APOA5 gene presented a 9% increase in circulating TG levels (p=0.002) and 10% decrease in HDLc levels (p=0.005). Such association of APOA5 towards dyslipidemia was accompanied by a 21% decrease of the CD4 T-cell count (p=0.024) and a 19% increase in CD8 T-cell count (p=0.002) in carriers of the rare allele in the APOA5 rs662799 polymorphism adjusted by age and gender. Patients carrying the rare allele in rs5128 (APOC3) had a 16% decrease in circulating CD4 T cells (p=0.029); patients carrying rs1800591 (MTP) had a 29% decrease in CD4 T cells and 14% decrease in CD8 T cells (p=0.018 and p=0.008, respectively); patients carrying the rare allele rs1800588 in HL had a 11% increase in CD4 T cells (p=0.043); and carriers of the rs145626 in the VLDLR gene had 10% decrease in CD4 circulating T cells (p=0.013).Variants in genes involved in the development of AD may also influence the immunological host-virus equilibrium in chronically HIV-infected subjects (2, 3).

Project description:BACKGROUND: Long term use of antiretroviral therapy (ART) in persons living with human immunodeficiency virus (PLWHIV) is associated with disturbances in blood lipids which should be monitored. More data on such disturbances are needed in Cameroon to persuade the country program to institute their routine monitoring. We then sought to determine the prevalence and timing of dyslipidaemia in PLWHIV and receiving ART in a predominantly rural Cameroonian setting. METHODS: A cross-sectional study conducted between August and October 2012 in HIV-infected persons aged 15 years or more and receiving first-line ART for at least six months at The Nkongsamba Regional Hospital in Cameroon. Lipid assays were carried out by enzymatic-linked colorimetric methods. A multiple logistic regression model was used to assess for factors related to dyslipidaemia. RESULTS: Included were 114 participants of whom 83 (72.8%) were females. Their median age was 43 years (IQR: 36-51) and their median CD4 count was 436 cells/?l (IQR: 275-585) after a median duration on ART of 36 months (IQR: 12-60). The prevalence of dyslipidaemia was 70.2%. Hypercholesterolaemia was observed in 34 (29.8%) patients. One-third of them had a high LDL-cholesterol level (LDL-c?130 mg/dl). Hypertriglyceridaemia (TG?150 mg/dl) was present in 59 (51.8%) cases. The proportion of patients with a low HDL-cholesterol (HDL-c<40 mg/dl) was 18.4% while those with a ratio of TC/HDL-c?5 were about 16.7%. A duration of 2-4 years on ART (adjusted Odd Ratio, aOR=5.22, 95% CI: 1.43-19.06, p=0.01), current smokers (aOR=15.94, 95% CI: 1.13-225.61, p=0.04) and a concurrent metabolic disease (aOR=12.54, 95% CI: 1.02-153.86, p=0.48) were independently associated with pro-atherogenic LDL-c values. Alcohol users had a more friendly LDL-c profile (aOR=0.24, 95% CI: 0.07-0.74, p=0.01). CONCLUSION: The study has demonstrated a high prevalence of dyslipidaemia in HIV-patients receiving first-line ART in a predominantly rural setting of Cameroon. There is a need for the country HIV program to institute laboratory monitoring of blood lipids in patients over two years on first line ART with a focus on smokers.

Dataset Information

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

Publications

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

Similar Datasets

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