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 language | English |
|---|---|
| Pages (from-to) | 22-28 |
| Number of pages | 7 |
| Journal | Atherosclerosis |
| Volume | 244 |
| DOIs | |
| Publication status | Published - 1 Jan 2016 |
| Externally published | Yes |
Keywords
- Dyslipidemias
- HDL metabolism
- HIV
- Lipids
- Lipoproteins
- MicroRNA
- Nef
Cite this
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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 journal › Article › Research › peer-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
PY - 2016/1/1
Y1 - 2016/1/1
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.
KW - Dyslipidemias
KW - HDL metabolism
KW - HIV
KW - Lipids
KW - Lipoproteins
KW - MicroRNA
KW - Nef
UR - http://www.scopus.com/inward/record.url?scp=84946615396&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2015.10.103
DO - 10.1016/j.atherosclerosis.2015.10.103
M3 - Article
VL - 244
SP - 22
EP - 28
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
ER -