MicroRNAs play an important role in the interaction between viruses and hosts. In this study, we found that the expression level of miR-33b-5p was markedly increased in human immunodeficiency virus type 1 (HIV-1)–infected cell lines and the serum of person with HIV-1. Further investigation revealed that the level of ATP-binding cassette transporter (ABCA1), which transports cholesterol between intracellular and extracellular compartments to maintain cholesterol homeostasis, was reduced in HIV-1–infected target cells, as the target gene of miR-33b-5p. Furthermore, HIV-1 infection stimulated abnormal lipid transport in macrophages, resulting in lipid accumulation in cells. These changes can be reversed by an miR-33b-5p inhibitor. We discovered a mechanism through which HIV-1 infection caused miR-33b-5p to target ABCA1 and caused aberrant lipid transport, providing a novel method for diagnosing and treating poor lipid metabolism in person with HIV-1.
Get full access to this article
View all access options for this article.
References
1.
AppayV, SauceD. Immune activation and inflammation in HIV-1 infection: Causes and consequences. J Pathol, 2008; 214(2):231–241; doi: 10.1002/path.2276
QiY, AilixireA, GaoYX, et al.Current situation and prospect of HIV-associated neurocognitive disorder research in China: Epidemiology, research, diagnosis, and treatment status. AIDS Rev, 2021; 23(2):74–81; doi: 10.24875/AIDSRev.20000044
4.
CihlarT, FordyceM. Current status and prospects of HIV treatment. Curr Opin Virol, 2016; 18:50–56; doi: 10.1016/j.coviro.2016.03.004
5.
BakerJV, HullsiekKH, SinghA, et al.Immunologic predictors of coronary artery calcium progression in a contemporary HIV cohort. AIDS, 2014; 28(6):831–840; doi: 10.1097/qad.0000000000000145
6.
So-ArmahK, BenjaminLA, BloomfieldGS, et al.HIV and cardiovascular disease. Lancet HIV, 2020; 7(4):e279–e293; doi: 10.1016/s2352-3018(20)30036-9
7.
LoJ. Dyslipidemia and lipid management in HIV-infected patients. Curr Opin Endocrinol Diabetes Obes, 2011; 18(2):144–147; doi:10.1097/MED.0b013e328344556e
8.
BowmanE, FunderburgNT. Lipidome abnormalities and cardiovascular disease risk in HIV infection. Curr HIV/AIDS Rep, 2019; 16(3):214–223; doi: 10.1007/s11904-019-00442-9
9.
FabianMR, SonenbergN, FilipowiczW. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem, 2010; 79:351–379; doi: 10.1146/annurev-biochem-060308-103103
SaliminejadK, Khorram KhorshidHR, Soleymani FardS, et al.An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J Cell Physiol, 2019; 234(5):5451–5465; doi: 10.1002/jcp.27486
13.
SuB, FuY, LiuY, et al.Potential application of microRNA profiling to the diagnosis and prognosis of HIV-1 infection. Front Microbiol, 2018; 9:3185; doi: 10.3389/fmicb.2018.03185
14.
PollerW, DimmelerS, HeymansS, et al.Non-coding RNAs in cardiovascular diseases: Diagnostic and therapeutic perspectives. Eur Heart J, 2018; 39(29):2704–2716; doi: 10.1093/eurheartj/ehx165
MaL, ShenCJ, Cohen ÉA, et al.miRNA-1236 inhibits HIV-1 infection of monocytes by repressing translation of cellular factor VprBP. PLoS One, 2014; 9(6):e99535; doi: 10.1371/journal.pone.0099535
19.
LuS, ZhuN, GuoW, et al.RNA-Seq revealed a circular RNA-microRNA-mRNA regulatory network in Hantaan virus infection. Front Cell Infect Microbiol, 2020; 10:97; doi: 10.3389/fcimb.2020.00097
20.
QiaoJ, PengQ, QianF, et al.HIV-1 Vpr protein upregulates microRNA-210-5p expression to induce G2 arrest by targeting TGIF2. PLoS One, 2021; 16(12):e0261971; doi: 10.1371/journal.pone.0261971
21.
PriceNL, RotllanN, Canfrán-DuqueA, et al.Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis. Cell Rep, 2017; 21(5):1317–1330: doi: 10.1016/j.celrep.2017.10.023
22.
JeongS, JunJH, KimJY, et al.Expression of miRNAs Targeting ATP binding cassette transporter 1 (ABCA1) among patients with significant carotid artery stenosis. Biomedicines, 2021; 9(8):920; doi: 10.3390/biomedicines9080920
23.
PhillipsMC. Is ABCA1 a lipid transfer protein?. J Lipid Res, 2018; 59(5):749–763; doi: 10.1194/jlr.R082313
24.
AdzhubeiAA, KulkarniA, TolstovaAP, et al.Direct interaction between ABCA1 and HIV-1 Nef: Molecular modeling and virtual screening for inhibitors. Comput Struct Biotechnol J, 2021; 19:3876–3884; doi: 10.1016/j.csbj.2021.06.050
25.
BabashamsiMM, KoukhalooSZ, HalalkhorS, et al.ABCA1 and metabolic syndrome; a review of the ABCA1 role in HDL-VLDL production, insulin-glucose homeostasis, inflammation and obesity. Diabetes Metab Syndr, 2019; 13(2):1529–1534; doi: 10.1016/j.dsx.2019.03.004
26.
PanP, ShenM, YuZ, et al.SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nat Commun, 2021; 12(1):4664; doi: 10.1038/s41467-021-25015-6
27.
Pilakka-KanthikeelS, SaiyedZM, NapuriJ, et al.MicroRNA: Implications in HIV, a brief overview. J Neurovirol, 2011; 17(5):416–423; doi: 10.1007/s13365-011-0046-1
28.
JiaM, ShaoY, HongK. MicroRNA 31 inhibits CD8(+) T-cell function by increasing its sensitivity to type I interferon signaling in chronic viral infection. Cell Mol Immunol, 2018; 15(5):533–535; doi: 10.1038/cmi.2017.99
29.
YangX, ZhaoQ, YinH, et al.MiR-33b-5p sensitizes gastric cancer cells to chemotherapy drugs via inhibiting HMGA2 expression. J Drug Target, 2017; 25(7):653–660; doi: 10.1080/1061186x.2017.1323220
30.
YangY, JiangH, XiaoL, et al.MicroRNA-33b-5p is overexpressed and inhibits GLUT4 by targeting HMGA2 in polycystic ovarian syndrome: An in vivo and in vitro study. Oncol Rep, 2018; 39(6):3073–3085; doi: 10.3892/or.2018.6375
31.
PrasadamI, BatraJ, PerryS, et al.Systematic identification, characterization and target gene analysis of microRNAs involved in osteoarthritis subchondral bone pathogenesis. Calcif Tissue Int, 2016; 99(1):43–55; doi: 10.1007/s00223-016-0125-7
32.
NagaoK, TomiokaM, UedaK. Function and regulation of ABCA1—Membrane meso-domain organization and reorganization. FEBS J, 2011; 278(18):3190–3203; doi: 10.1111/j.1742-4658.2011.08170.x
LowH, HoangA, PushkarskyT, et al.HIV disease, metabolic dysfunction and atherosclerosis: A three year prospective study. PLoS One, 2019; 14(4):e0215620; doi: 10.1371/journal.pone.0215620
35.
IslamFM, WuJ, JanssonJ, et al.Relative risk of cardiovascular disease among people living with HIV: A systematic review and meta-analysis. HIV Med, 2012; 13(8):453–468; doi: 10.1111/j.1468-1293.2012.00996.x
36.
Friis-MøllerN, ReissP, SabinCA, et al.Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med, 2007; 356(17):1723–1735; doi: 10.1056/NEJMoa062744
37.
da CunhaJ, Ferreira MaselliLM, TreitingerA, et al.Serum levels of IgG antibodies against oxidized LDL and atherogenic indices in HIV-1-infected patients treated with protease inhibitors. Clin Chem Lab Med, 2013; 51(2):371–378, doi:10.1515/cclm-2012-0225
38.
SankatsingRR, WitFW, VogelM, et al.Increased carotid intima-media thickness in HIV patients treated with protease inhibitors as compared to non-nucleoside reverse transcriptase inhibitors. Atherosclerosis, 2009; 202(2):589–595; doi: 10.1016/j.atherosclerosis.2008.05.028
39.
WangX, ChaiH, YaoQ, et al.Molecular mechanisms of HIV protease inhibitor-induced endothelial dysfunction. J Acquir Immune Defic Syndr, 2007; 44(5):493–499; doi: 10.1097/QAI.0b013e3180322542
40.
RiddlerSA, LiX, OtvosJ, et al.Antiretroviral therapy is associated with an atherogenic lipoprotein phenotype among HIV-1-infected men in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr, 2008; 48(3):281–288; doi: 10.1097/QAI.0b013e31817bbbf0
41.
BarwariT, JoshiA, MayrM. MicroRNAs in cardiovascular disease. J Am Coll Cardiol, 2016; 68(23):2577–2584; doi: 10.1016/j.jacc.2016.09.945
42.
TianM, ZhouF, TengZ, et al.Curcumin ameliorates lipid metabolic disorder and cognitive dysfunction via the ABCA1 transmembrane transport system in APP/PS1 double transgenic mice. J Integr Neurosci, 2021; 20(4):895–903; doi: 10.31083/j.jin2004091
