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

Hann Low, Lesley Cheng, Maria Silvana Di Yacovo, Melissa J. Churchill, Peter Meikle, Michael Bukrinsky, Andrew F Hill, Dmitri Sviridov

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)22-28
Number of pages7
JournalAtherosclerosis
Volume244
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

Keywords

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

Cite this

Low, Hann ; Cheng, Lesley ; Di Yacovo, Maria Silvana ; Churchill, Melissa J. ; Meikle, Peter ; Bukrinsky, Michael ; Hill, Andrew F ; Sviridov, Dmitri. / Lipid metabolism in patients infected with Nef-deficient HIV-1 strain. In: Atherosclerosis. 2016 ; Vol. 244. pp. 22-28.
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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-na{\"i}ve 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",
author = "Hann Low and Lesley Cheng and {Di Yacovo}, {Maria Silvana} and Churchill, {Melissa J.} and Peter Meikle and Michael Bukrinsky and Hill, {Andrew F} and Dmitri Sviridov",
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Lipid metabolism in patients infected with Nef-deficient HIV-1 strain. / Low, Hann; Cheng, Lesley; Di Yacovo, Maria Silvana; Churchill, Melissa J.; Meikle, Peter; Bukrinsky, Michael; Hill, Andrew F; Sviridov, Dmitri.

In: Atherosclerosis, Vol. 244, 01.01.2016, p. 22-28.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Lipid metabolism in patients infected with Nef-deficient HIV-1 strain

AU - Low, Hann

AU - Cheng, Lesley

AU - Di Yacovo, Maria Silvana

AU - Churchill, Melissa J.

AU - Meikle, Peter

AU - Bukrinsky, Michael

AU - Hill, Andrew F

AU - Sviridov, Dmitri

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N2 - 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.

AB - 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.

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KW - HDL metabolism

KW - HIV

KW - Lipids

KW - Lipoproteins

KW - MicroRNA

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SN - 0021-9150

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