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Review Article

Cholesterol: A friend to viruses

& ORCID Icon
Pages 248-262 | Received 17 Sep 2023, Accepted 28 Jan 2024, Published online: 19 Feb 2024

References

  • Chu BB, Liao YC, Qi W, et al. Cholesterol transport through lysosome-peroxisome membrane contacts. Cell. 2015;161(2):291–306. doi:10.1016/j.cell.2015.02.019.
  • Di Paolo G, Kim TW. Linking lipids to Alzheimer’s disease: Cholesterol and beyond. Nat Rev Neurosci. 2011;12(5):284–296. doi:10.1038/nrn3012.
  • Goossens P, Rodriguez-Vita J, Etzerodt A, et al. Membrane cholesterol efflux drives tumor-associated macrophage reprogramming and tumor progression. Cell Metab. 2019;29(6):1376–1389.e4. e1374. doi:10.1016/j.cmet.2019.02.016.
  • Hoppstädter J, Dembek A, Höring M, et al. Dysregulation of cholesterol homeostasis in human lung cancer tissue and tumour-associated macrophages. EBioMed. 2021;72:103578. doi:10.1016/j.ebiom.2021.103578.
  • Sag D, Cekic C, Wu R, et al. The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity. Nat Commun. 2015;6(1):6354. doi:10.1038/ncomms7354.
  • Mackenzie JM, Khromykh AA, Parton RG. Cholesterol manipulation by West Nile virus perturbs the cellular immune response. Cell Host Microbe. 2007;2(4):229–239. doi:10.1016/j.chom.2007.09.003.
  • Blanc M, Hsieh WY, Robertson KA, et al. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol. 2011;9(3):e1000598. doi:10.1371/journal.pbio.1000598.
  • Petersen J, Drake MJ, Bruce EA, et al. The major cellular sterol regulatory pathway is required for Andes virus infection. PLoS Pathog. 2014;10(2):e1003911. doi:10.1371/journal.ppat.1003911.
  • Kapadia SB, Chisari FV. Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci USA. 2005;102(7):2561–2566. doi:10.1073/pnas.0409834102.
  • Osuna-Ramos JF, Reyes-Ruiz JM, Del Angel, RM. The role of host cholesterol during flavivirus infection. Front Cell Infect Microbiol. 2018;8:388. doi:10.3389/fcimb.2018.00388.
  • Nagy PD. Viral sensing of the subcellular environment regulates the assembly of new viral replicase complexes during the course of infection. J Virol. 2015;89(10):5196–5199. doi:10.1128/JVI.02973-14.
  • Yuan S, Chu H, Chan JF, et al. SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target. Nat Commun. 2019;10(1):120. doi:10.1038/s41467-018-08015-x.
  • Ilnytska O, Santiana M, Hsu NY, et al. Enteroviruses harness the cellular endocytic machinery to remodel the host cell cholesterol landscape for effective viral replication. Cell Host Microbe. 2013;14(3):281–293. doi:10.1016/j.chom.2013.08.002.
  • Wang C, Gale MJr., Keller BC, et al. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell. 2005;18(4):425–434. doi:10.1016/j.molcel.2005.04.004.
  • Cui HL, Grant A, Mukhamedova N, et al. HIV-1 Nef mobilizes lipid rafts in macrophages through a pathway that competes with ABCA1-dependent cholesterol efflux. J Lipid Res. 2012;53(4):696–708. doi:10.1194/jlr.M023119.
  • York AG, Williams KJ, Argus JP, et al. Limiting cholesterol biosynthetic flux spontaneously engages type I IFN signaling. Cell. 2015;163(7):1716–1729. doi:10.1016/j.cell.2015.11.045.
  • Gilbert C, Bergeron M, Méthot S, et al . Statins could be used to control replication of some viruses, including HIV-1. Viral Immunol. 2005;18(3):474–489. doi:10.1089/vim.2005.18.474.
  • Rzouq F, Alahdab F, Olyaee M. Statins and hepatitis C virus infection: An old therapy with new scope. Am J Med Sci. 2014;348(5):426–430. doi:10.1097/MAJ.0000000000000291.
  • Sezgin E, Levental I, Mayor S, Eggeling C. The mystery of membrane organization: Composition, regulation and roles of lipid rafts. Nat Rev Mol Cell Biol. 2017;18(6):361–374. doi:10.1038/nrm.2017.16.
  • Kuzu OF, Noory MA, Robertson GP. The role of cholesterol in cancer. Cancer Res. 2016;76(8):2063–2070. doi:10.1158/0008-5472.CAN-15-2613.
  • Burnett JR, Hooper AJ, Hegele RA. Remnant cholesterol and atherosclerotic cardiovascular disease risk. J Am Coll Cardiol. 2020;76(23):2736–2739. doi:10.1016/j.jacc.2020.10.029.
  • Eberlé D, Hegarty B, Bossard P, Ferré P, Foufelle F. SREBP transcription factors: Master regulators of lipid homeostasis. Biochimie. 2004;86(11):839–848. doi:10.1016/j.biochi.2004.09.018.
  • Goldstein JL, DeBose-Boyd RA, Brown MS. Protein sensors for membrane sterols. Cell. 2006;124(1):35–46. doi:10.1016/j.cell.2005.12.022.
  • Brown AJ, Sun L, Feramisco JD, Brown MS, Goldstein JL. Cholesterol addition to ER membranes alters conformation of SCAP, the SREBP escort protein that regulates cholesterol metabolism. Mol Cell. 2002;10(2):237–245. doi:10.1016/s1097-2765(02)00591-9.
  • Brown MS, Radhakrishnan A, Goldstein JL. Retrospective on cholesterol homeostasis: The central role of scap. Annu Rev Biochem. 2018;87(1):783–807. doi:10.1146/annurev-biochem-062917-011852.
  • Lee SJ, Sekimoto T, Yamashita E, et al. The structure of importin-ß bound to SREBP-2 nuclear import of a transcription factor. Science. 2003;302(5650):1571–1575. doi:10.1126/science.1088372.
  • Altmann SW, Davis HJ, Zhu LJ, et al. Niemann–Pick C1 like 1 protein is critical for intestinal cholesterol absorption. Science. 2004;303(5661):1201–1204. doi:10.1126/science.1093131.
  • Zhang JH, Ge L, Qi W, et al. The N-terminal domain of NPC1L1 protein binds cholesterol and plays essential roles in cholesterol uptake. J Biol Chem. 2011;286(28):25088–25097. doi:10.1074/jbc.M111.244475.
  • Li P-S, Fu Z-Y, Zhang Y-Y, et al. The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1. Nat Med. 2013;20(1):80–86. doi:10.1038/nm.3417.
  • Garcia CK, Wilund K, Arca M, et al. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science. 2001;292(5520):1394–1398. doi:10.1126/science.1060458.
  • Kwon HJ, Abi-Mosleh L, Wang ML, et al. Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol. Cell. 2009;137(7):1213–1224. doi:10.1016/j.cell.2009.03.049.
  • Chen L, Zhao ZW, Zeng PH, Zhou YJ, Yin WJ. Molecular mechanisms for ABCA1-mediated cholesterol efflux. Cell Cycle. 2022;21(11):1121–1139. doi:10.1080/15384101.2022.2042777.
  • Rosenson RS, Brewer HBJr., Davidson WS, et al. Cholesterol efflux and atheroprotection: Advancing the concept of reverse cholesterol transport. Circulation. 2012;125(15):1905–1919. doi:10.1161/CIRCULATIONAHA.111.066589.
  • Wang N, Silver DL, Thiele C, Tall AR. ATP-binding cassette transporter A1 (ABCA1) functions as a cholesterol efflux regulatory protein. J Biol Chem. 2001;276(26):23742–23747. doi:10.1074/jbc.M102348200.
  • Tarling EJ, Edwards PA. ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter. Proc Natl Acad Sci USA. 2011;108(49):19719–19724. doi:10.1073/pnas.1113021108.
  • Kennedy MA, Barrera GC, Nakamura K, et al. ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab. 2005;1(2):121–131. doi:10.1016/j.cmet.2005.01.002.
  • Kobayashi A, Takanezawa Y, Hirata T, et al. Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1. J Lipid Res. 2006;47(8):1791–1802. doi:10.1194/jlr.M500546-JLR200.
  • Graf GA, Yu L, Li WP, et al. ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J Biol Chem. 2003;278(48):48275–48282. doi:10.1074/jbc.M310223200.
  • Rogers MA, Liu J, Song BL, Li BL, Chang CC, Chang, TY. Acyl-CoA:cholesterol acyltransferases (ACATs/SOATs): Enzymes with multiple sterols as substrates and as activators. J Steroid Biochem Mol Biol. 2015;151:102–107. doi:10.1016/j.jsbmb.2014.09.008.
  • Chang TY, Chang CC, Ohgami N, Yamauchi Y. Cholesterol sensing, trafficking, and esterification. Annu Rev Cell Dev Biol. 2006;22(1):129–157. doi:10.1146/annurev.cellbio.22.010305.104656.
  • Yu C, Chen J, Lin S, Liu J, Chang CC, Chang, TY. Human acyl-CoA:cholesterol acyltransferase-1 is a homotetrameric enzyme in intact cells and in vitro. J Biol Chem. 1999;274(51):36139–36145. doi:10.1074/jbc.274.51.36139.
  • Chang CC, Sakashita N, Ornvold K, et al. Immunological quantitation and localization of ACAT-1 and ACAT-2 in human liver and small intestine. J Biol Chem. 2000;275(36):28083–28092. doi:10.1074/jbc.M003927200.
  • Liu J, Chang CC, Westover EJ, Covey DF, Chang, TY. Investigating the allosterism of acyl-CoA:cholesterol acyltransferase (ACAT) by using various sterols: In vitro and intact cell studies. Biochem J. 2005;391(Pt 2):389–397. doi:10.1042/BJ20050428.
  • Romeo S. ACAT2 as a novel therapeutic target to treat fatty liver disease. J Intern Med. 2022;292(2):175–176. doi:10.1111/joim.13460.
  • Parini P, Davis M, Lada AT, et al. ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver. Circulation. 2004;110(14):2017–2023. doi:10.1161/01.CIR.0000143163.76212.0B.
  • Cases S, Novak S, Zheng YW, et al. ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase. Its cloning, expression, and characterization. J Biol Chem. 1998;273(41):26755–26764. doi:10.1074/jbc.273.41.26755.
  • Branche E, Wang YT, Viramontes KM, et al. SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus. Nat Commun. 2022;13(1):5341. doi:10.1038/s41467-022-33041-1.
  • Lee W, Ahn JH, Park HH, et al. COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm. Signal Transduct Target Ther. 2020;5(1):186. doi:10.1038/s41392-020-00292-7.
  • Li M, Wang Q, Liu SA, et al. MicroRNA-185-5p mediates regulation of SREBP2 expression by hepatitis C virus core protein. World J Gastroenterol. 2015;21(15):4517–4525. doi:10.3748/wjg.v21.i15.4517.
  • Zhang F, Sodroski C, Cha H, Li Q, Liang TJ. Infection of hepatocytes with HCV increases cell surface levels of heparan sulfate proteoglycans, uptake of cholesterol and lipoprotein, and virus entry by up-regulating SMAD6 and SMAD7. Gastroenterology. 2017;152(1):257–270.e7. e257. doi:10.1053/j.gastro.2016.09.033.
  • Yang Y, Li M, Ma Y, et al. LncRNA NEAT1 potentiates SREBP2 activity to promote inflammatory macrophage activation and limit Hantaan virus propagation. Front Microbiol. 2022;13:849020. doi:10.3389/fmicb.2022.849020.
  • Soto-Acosta R, Mosso C, Cervantes-Salazar M, et al. The increase in cholesterol levels at early stages after dengue virus infection correlates with an augment in LDL particle uptake and HMG-CoA reductase activity. Virology. 2013;442(2):132–147. doi:10.1016/j.virol.2013.04.003.
  • Geier A. Hepatitis B virus: The "metabolovirus" highjacks cholesterol and bile acid metabolism. Hepatology. 2014;60(5):1458–1460. doi:10.1002/hep.27224.
  • Zheng YH, Plemenitas A, Fielding CJ, et al. Nef increases the synthesis of and transports cholesterol to lipid rafts and HIV-1 progeny virions. Proc Natl Acad Sci USA. 2003;100(14):8460–8465. doi:10.1073/pnas.1437453100.
  • El Khoury P, Ghislain M, Villard EF, et al. Plasma cholesterol efflux capacity from human THP-1 macrophages is reduced in HIV-infected patients: Impact of HAART. J Lipid Res. 2015;56(3):692–702. doi:10.1194/jlr.M054510.
  • Mujawar Z, Rose H, Morrow MP, et al. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages. PLoS Biol. 2006;4(11):e365. doi:10.1371/journal.pbio.0040365.
  • Ke W, Zhou Y, Lai Y, Long S, Fang L, Xiao S. Porcine reproductive and respiratory syndrome virus nsp4 positively regulates cellular cholesterol to inhibit type I interferon production. Redox Biol. 2022;49:102207. doi:10.1016/j.redox.2021.102207.
  • Zou X, Lin F, Yang Y, et al. Cholesterol biosynthesis modulates CSFV replication. Viruses. 2022;14(7):1450. doi:10.3390/v14071450.
  • Xiao J, Li W, Zheng X, et al. Targeting 7-dehydrocholesterol reductase integrates cholesterol metabolism and IRF3 activation to eliminate infection. Immunity. 2020;52(1):109–122.e6. doi:10.1016/j.immuni.2019.11.015.
  • Blanc M, Hsieh WY, Robertson KA, et al. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity. 2013;38(1):106–118. doi:10.1016/j.immuni.2012.11.004.
  • Radenkovic D, Chawla S, Pirro M, et al. Cholesterol in relation to COVID-19: Should we care about it? J Clin Med. 2020;9(6):1909. doi:10.3390/jcm9061909.
  • Kočar E, Režen T, Rozman D. Cholesterol, lipoproteins, and COVID-19: Basic concepts and clinical applications. Biochim Biophys Acta Mol Cell Biol Lipids. 2021;1866(2):158849. doi:10.1016/j.bbalip.2020.158849.
  • Wei C, Wan L, Yan Q, et al. HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry. Nat Metab. 2020;2(12):1391–1400. doi:10.1038/s42255-020-00324-0.
  • Yin J, Glende J, Schwegmann-Wessels C, et al. Cholesterol is important for a post-adsorption step in the entry process of transmissible gastroenteritis virus. Antiviral Res. 2010;88(3):311–316. doi:10.1016/j.antiviral.2010.10.002.
  • Zeisel MB, Felmlee DJ, Baumert TF. Hepatitis C virus entry. Curr Top Microbiol Immunol. 2013;369:87–112. doi:10.1007/978-3-642-27340-7_4.
  • Felmlee DJ, Hafirassou ML, Lefevre M, Baumert TF, Schuster C. Hepatitis C virus, cholesterol and lipoproteins–impact for the viral life cycle and pathogenesis of liver disease. Viruses. 2013;5(5):1292–1324. doi:10.3390/v5051292.
  • Lee J, Kreutzberger AJB, Odongo L, et al. Ebola virus glycoprotein interacts with cholesterol to enhance membrane fusion and cell entry. Nat Struct Mol Biol. 2021;28(2):181–189. doi:10.1038/s41594-020-00548-4.
  • San-Juan-Vergara H, Sampayo-Escobar V, Reyes N, et al. Cholesterol-rich microdomains as docking platforms for respiratory syncytial virus in normal human bronchial epithelial cells. J Virol. 2012;86(3):1832–1843. doi:10.1128/JVI.06274-11.
  • Contreras EM, Johnston GP, Buchholz DW, et al. Roles of cholesterol in early and late steps of the Nipah virus membrane fusion cascade. J Virol. 2021;95(6):e02323-20. doi:10.1128/JVI.02323-20.
  • Wudiri GA, Schneider SM, Nicola AV. Herpes simplex virus 1 envelope cholesterol facilitates membrane fusion. Front Microbiol. 2017;8:2383. doi:10.3389/fmicb.2017.02383.
  • Wudiri GA, Nicola AV. Cellular cholesterol facilitates the postentry replication cycle of herpes simplex virus 1. J Virol. 2017;91(14):e00445-17. doi:10.1128/JVI.00445-17.
  • Kremer EJ, Haspot F, Lavault A, et al. Human cytomegalovirus entry into dendritic cells occurs via a macropinocytosis-like pathway in a pH-independent and cholesterol-dependent manner. PLoS One. 2012;7(4):e34795. doi:10.1371/journal.pone.0034795.
  • Raghu H, Sharma-Walia N, Veettil MV, et al. Lipid rafts of primary endothelial cells are essential for Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8-induced phosphatidylinositol 3-kinase and RhoA-GTPases critical for microtubule dynamics and nuclear delivery of viral DNA but dispensable for binding and entry. J Virol. 2007;81(15):7941–7959. doi:10.1128/jvi.02848-06.
  • Wang S, Li W, Hui H, et al. Cholesterol 25-Hydroxylase inhibits SARS-CoV-2 and other coronaviruses by depleting membrane cholesterol. EMBO J. 2020;39(21):e106057. doi:10.15252/embj.2020106057.
  • Liu SY, Aliyari R, Chikere K, et al. Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity. 2013;38(1):92–105. doi:10.1016/j.immuni.2012.11.005.
  • Koonin EV, Dolja VV, Krupovic M, et al. Global organization and proposed megataxonomy of the virus world. Microbiol Mol Biol Rev. 2020;84(2):e00061–00019. doi:10.1128/MMBR.00061-19.
  • Kausar S, Said Khan F, Ishaq Mujeeb Ur Rehman M, et al. A review: Mechanism of action of antiviral drugs. Int J Immunopathol Pharmacol. 2021;35:20587384211002621. doi:10.1177/:20587384211002621.
  • Dai J, Wang H, Liao Y, et al. Coronavirus infection and cholesterol metabolism. Front Immunol. 2022;13:791267. doi:10.3389/fimmu.2022.791267.
  • Ohashi H, Wang F, Stappenbeck F, et al. Identification of anti-severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) oxysterol derivatives in vitro. Int J Mol Sci. 2021;22(6):3163. doi:10.3390/ijms22063163.
  • Ishikawa-Sasaki K, Nagashima S, Taniguchi K, et al. Model of OSBP-mediated cholesterol supply to aichi virus RNA replication sites involving protein-protein interactions among viral proteins, ACBD3, OSBP, VAP-A/B, and SAC1. J Virol. 2018;92(8):e01952-17. doi:10.1128/JVI.01952-17.
  • Xu N, Shen N, Wang X, et al. Protein prenylation and human diseases: A balance of protein farnesylation and geranylgeranylation. Sci China Life Sci. 2015;58(4):328–335. doi:10.1007/s11427-015-4836-1.
  • Brown DA, London E. Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem. 2000;275(23):17221–17224. doi:10.1074/jbc.R000005200.
  • Bajimaya S, Hayashi T, Frankl T, et al. Cholesterol reducing agents inhibit assembly of type I parainfluenza viruses. Virology. 2017;501:127–135. doi:10.1016/j.virol.2016.11.011.
  • Nayak DP, Hui EK, Barman S. Assembly and budding of influenza virus. Virus Res. 2004;106(2):147–165. doi:10.1016/j.virusres.2004.08.012.
  • Brown G, Jeffree CE, McDonald T, et al. Analysis of the interaction between respiratory syncytial virus and lipid-rafts in Hep2 cells during infection. Virology. 2004;327(2):175–185. doi:10.1016/j.virol.2004.06.038.
  • Chang TH, Segovia J, Sabbah A, et al. Cholesterol-rich lipid rafts are required for release of infectious human respiratory syncytial virus particles. Virology. 2012;422(2):205–213. doi:10.1016/j.virol.2011.10.029.
  • Bajimaya S, Frankl T, Hayashi T, Takimoto T. Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses. Virology. 2017;510:234–241. doi:10.1016/j.virol.2017.07.024.
  • Mazière JC, Landureau JC, Giral P, et al. Lovastatin inhibits HIV-1 expression inH9 human T lymphocytes cultured in cholesterol-poor medium. Biomed Pharmacother. 1994;48(2):63–67. doi:10.1016/0753-3322(94)90077-9.
  • Miyanari Y, Atsuzawa K, Usuda N, et al. The lipid droplet is an important organelle for hepatitis C virus production. Nat Cell Biol. 2007;9(9):1089–1097. doi:10.1038/ncb1631.
  • Campbell SM, Crowe SM, Mak J. Lipid rafts and HIV-1: From viral entry to assembly of progeny virions. J Clin Virol. 2001;22(3):217–227. doi:10.1016/s1386-6532(01)00193-7.
  • Liu B, Ma Y, Huang Y, et al. Inhibition of human cytomegalovirus particle maturation by activation of liver X receptor. Front Microbiol. 2022;13:846386. doi:10.3389/fmicb.2022.846386.
  • Li YJ, Chen CY, Yang JH, Chiu YF. Modulating cholesterol-rich lipid rafts to disrupt influenza A virus infection. Front Immunol. 2022;13:982264. doi:10.3389/fimmu.2022.982264.
  • Martyna A, Bahsoun B, Madsen JJ, et al. Cholesterol alters the orientation and activity of the influenza virus M2 amphipathic helix in the membrane. J Phys Chem B. 2020;124(31):6738–6747. doi:10.1021/acs.jpcb.0c03331.
  • Lu YE, Kielian M. Semliki forest virus budding: Assay, mechanisms, and cholesterol requirement. J Virol. 2000;74(17):7708–7719. doi:10.1128/jvi.74.17.7708-7719.2000.
  • Ono A, Freed EO. Plasma membrane rafts play a critical role in HIV-1 assembly and release. Proc Natl Acad Sci USA. 2001;98(24):13925–13930. doi:10.1073/pnas.241320298.
  • Feng P, Wang X, Zhu N, et al. Mono-ubiquitylated ORF45 mediates association of KSHV particles with internal lipid rafts for viral assembly and egress. PLoS Pathog. 2015;11(12):e1005332. doi:10.1371/journal.ppat.1005332.
  • Kuhn RJ, Soto-Acosta R, Bautista-Carbajal P, et al. DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target. PLoS Pathog. 2017;13(4):e1006257. doi:10.1371/journal.ppat.1006257.
  • Dorner M, Horwitz JA, Robbins JB, et al. A genetically humanized mouse model for hepatitis C virus infection. Nature. 2011;474(7350):208–211. doi:10.1038/nature10168.
  • Sainz B, Barretto N, Martin DN, et al. Identification of the Niemann–Pick C1–like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nat Med. 2012;18(2):281–285. doi:10.1038/nm.2581.
  • Li C, Deng YQ, Wang S, et al. 25-Hydroxycholesterol protects host against Zika virus infection and its associated microcephaly in a mouse model. Immunity. 2017;46(3):446–456. doi:10.1016/j.immuni.2017.02.012.
  • Civra A, Colzani M, Cagno V, et al. Modulation of cell proteome by 25-hydroxycholesterol and 27-hydroxycholesterol: A link between cholesterol metabolism and antiviral defense. Free Radic Biol Med. 2020;149:30–36. doi:10.1016/j.freeradbiomed.2019.08.031.
  • Wang Y, Li G-L, Qi Y-L, et al. Pseudorabies virus inhibits expression of liver X receptors to assist viral infection. Viruses. 2022;14(3):514. doi:10.3390/v14030514.
  • Fasolato S, Pigozzo S, Pontisso P, et al. PCSK9 levels are raised in chronic HCV patients with hepatocellular carcinoma. J Clin Med. 2020;9(10):3134. doi:10.3390/jcm9103134.
  • Gan ES, Tan HC, Le DHT, et al. Dengue virus induces PCSK9 expression to alter antiviral responses and disease outcomes. J Clin Invest. 2020;130(10):5223–5234. doi:10.1172/JCI137536.
  • Li G, Su B, Fu P, et al. NPC1-regulated dynamic of clathrin-coated pits is essential for viral entry. Sci China Life Sci. 2021;65(2):341–361. doi:10.1007/s11427-021-1929-y.
  • Carette JE, Raaben M, Wong AC, et al. Ebola virus entry requires the cholesterol transporter Niemann–Pick C1. Nature. 2011;477(7364):340–343. doi:10.1038/nature10348.
  • Wu C-Y, Chang C-Y, Ma H-H, et al. Squalene-adjuvanted H7N9 virus vaccine induces robust humoral immune response against H7N9 and H7N7 viruses. Vaccine. 2014;32(35):4485–4494. doi:10.1016/j.vaccine.2014.06.043.
  • Sangeetha B, Krishnamoorthy AS, Sharmila D, et al. Molecular modelling of coat protein of the Groundnut bud necrosis tospovirus and its binding with Squalene as an antiviral agent: In vitro and in silico docking investigations. Int J Biol Macromol. 2021;189:618–634. doi:10.1016/j.ijbiomac.2021.08.143.
  • Villareal VA, Fu D, Costello DA, et al. Hepatitis C virus selectively alters the intracellular localization of desmosterol. ACS Chem Biol. 2016;11(7):1827–1833. doi:10.1021/acschembio.6b00324.
  • Costello DA, Villareal VA, Yang, PL. Desmosterol increases lipid bilayer fluidity during hepatitis C virus infection. ACS Infect Dis. 2016;2(11):852–862. doi:10.1021/acsinfecdis.6b00086.
  • Rodgers MA, Villareal VA, Schaefer EA, et al. Lipid metabolite profiling identifies desmosterol metabolism as a new antiviral target for hepatitis C virus. J Am Chem Soc. 2012;134(16):6896–6899. doi:10.1021/ja207391q.
  • Wudiri GA, Pritchard SM, Li H, et al. Molecular requirement for sterols in herpes simplex virus entry and infectivity. J Virol. 2014;88(23):13918–13922. doi:10.1128/jvi.01615-14.
  • Lembo D, Cagno V, Civra A, Poli G. Oxysterols: An emerging class of broad spectrum antiviral effectors. Mol Aspects Med. 2016;49:23–30. doi:10.1016/j.mam.2016.04.003.
  • Shrivastava-Ranjan P, Bergeron É, Chakrabarti AK, et al. 25-Hydroxycholesterol inhibition of Lassa virus infection through aberrant GP1 glycosylation. mBio. 2016;7(6):e01808-16. doi:10.1128/mBio.01808-16.
  • Marcello A, Civra A, Milan Bonotto R, et al. The cholesterol metabolite 27-hydroxycholesterol inhibits SARS-CoV-2 and is markedly decreased in COVID-19 patients. Redox Biol. 2020;36:101682. doi:10.1016/j.redox.2020.101682.
  • Zu S, Deng YQ, Zhou C, et al. 25-Hydroxycholesterol is a potent SARS-CoV-2 inhibitor. Cell Res. 2020;30(11):1043–1045. doi:10.1038/s41422-020-00398-1.
  • Ablasser A, Hur S. Regulation of cGAS- and RLR-mediated immunity to nucleic acids. Nat Immunol. 2020;21(1):17–29. doi:10.1038/s41590-019-0556-1.
  • Willemsen L, Chen HJ, van Roomen C, et al. Monocyte and macrophage lipid accumulation results in down-regulated type-I interferon responses. Front Cardiovasc Med. 2022;9:829877. doi:10.3389/fcvm.2022.829877.
  • Wang M, Casey PJ. Protein prenylation: Unique fats make their mark on biology. Nat Rev Mol Cell Biol. 2016;17(2):110–122. doi:10.1038/nrm.2015.11.
  • Yang S, Harding AT, Sweeney C, et al. Control of antiviral innate immune response by protein geranylgeranylation. Sci Adv. 2019;5(5):eaav7999. doi:10.1126/sciadv.aav7999.
  • Wang Y, Wang Y, Ding L, et al. Tim-4 reprograms cholesterol metabolism to suppress antiviral innate immunity by disturbing the Insig1-SCAP interaction in macrophages. Cell Rep. 2022;41(9):111738. doi:10.1016/j.celrep.2022.111738.
  • Lange PT, Darrah EJ, Vonderhaar EP, et al. Type I interferon counteracts antiviral effects of statins in the context of gammaherpesvirus infection. J Virol. 2016;90(7):3342–3354. doi:10.1128/JVI.02277-15.
  • del Real G, Jiménez-Baranda S, Mira E, et al. Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med. 2004;200(4):541–547. doi:10.1084/jem.20040061.
  • Gower TL, Graham BS. Antiviral activity of lovastatin against respiratory syncytial virus in vivo and in vitro. Antimicrob Agents Chemother. 2001;45(4):1231–1237. doi:10.1128/AAC.45.4.1231-1237.2001.
  • Ikeda M, Abe K, Yamada M, et al. Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology. 2006;44(1):117–125. doi:10.1002/hep.21232.
  • Shrivastava-Ranjan P, Flint M, Bergeron E, et al. Statins suppress ebola virus infectivity by interfering with glycoprotein processing. mBio. 2018;9(3). doi:10.1128/mBio.00660-18.
  • Rothwell C, Lebreton A, Young Ng C, et al. Cholesterol biosynthesis modulation regulates dengue viral replication. Virology. 2009;389(1–2):8–19. doi:10.1016/j.virol.2009.03.025.
  • Martínez-Gutierrez M, Castellanos JE, Gallego-Gómez JC. Statins reduce dengue virus production via decreased virion assembly. Intervirology. 2011;54(4):202–216. doi:10.1159/000321892.
  • Troeman DP, Postma DF, van Werkhoven CH, et al. The immunomodulatory effects of statins in community-acquired pneumonia: A systematic review. J Infect. 2013;67(2):93–101. doi:10.1016/j.jinf.2013.04.015.
  • Kwong JC, Li P, Redelmeier DA. Influenza morbidity and mortality in elderly patients receiving statins: A cohort study. PLoS One. 2009;4(11):e8087. doi:10.1371/journal.pone.0008087.
  • Atamna A, Babitch T, Bracha M, et al. Statins and outcomes of hospitalized patients with laboratory-confirmed 2017-2018 influenza. Eur J Clin Microbiol Infect Dis. 2019;38(12):2341–2348. doi:10.1007/s10096-019-03684-y.
  • Kondo C, Atsukawa M, Tsubota A, et al. An open-label randomized controlled study of pegylated interferon/ribavirin combination therapy for chronic hepatitis C with versus without fluvastatin. J Viral Hepat. 2012;19(9):615–622. doi:10.1111/j.1365-2893.2011.01584.x.
  • Sezaki H, Suzuki F, Akuta N, et al. An open pilot study exploring the efficacy of fluvastatin, pegylated interferon and ribavirin in patients with hepatitis C virus genotype 1b in high viral loads. Intervirology. 2009;52(1):43–48. doi:10.1159/000213504.
  • Yang YH, Chen WC, Tsan YT, et al. Statin use and the risk of cirrhosis development in patients with hepatitis C virus infection. J Hepatol. 2015;63(5):1111–1117. doi:10.1016/j.jhep.2015.07.006.
  • Ma X, Sun D, Li C, Ying J, Yan Y. Statin use and virus-related cirrhosis: A systemic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2017;41(5):533–542. doi:10.1016/j.clinre.2017.07.004.
  • Choi WM, Kim HJ, Jo AJ, et al. Association of aspirin and statin use with the risk of liver cancer in chronic hepatitis B: A nationwide population-based study. Liver Int. 2021;41(11):2777–2785. doi:10.1111/liv.15011.
  • Huang W, Xiao J, Ji J, Chen L. Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study. Elife. 2021;10:e73873. doi:10.7554/eLife.73873.
  • Zhang XJ, Qin JJ, Cheng X, et al. In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19. Cell Metab. 2020;32(2):176–187.e4. doi:10.1016/j.cmet.2020.06.015.
  • Vahedian-Azimi A, Mohammadi SM, Banach M, et al. Improved COVID-19 outcomes following statin therapy: An updated systematic review and meta-analysis. Biomed Res Int. 2021;2021:1901772. doi:10.1155/2021/1901772.
  • Assefi M, Bijan Rostami R, Ebrahimi M, et al. Potential use of the cholesterol transfer inhibitor U18666A as an antiviral drug for research on various viral infections. Microb Pathog. 2023;179:106096. doi:10.1016/j.micpath.2023.106096.
  • Glitscher M, Martín DH, Woytinek K, et al. Targeting cholesterol metabolism as efficient antiviral strategy against the hepatitis E virus. Cell Mol Gastroenterol Hepatol. 2021;12(1):159–180. doi:10.1016/j.jcmgh.2021.02.002.
  • Pawar A, Pal A, Goswami K, et al. Molecular basis of quercetin as a plausible common denominator of macrophage-cholesterol-fenofibrate dependent potential COVID-19 treatment axis. Results Chem. 2021;3:100148. doi:10.1016/j.rechem.2021.
  • Pollock S, Nichita NB, Böhmer A, et al. Polyunsaturated liposomes are antiviral against hepatitis B and C viruses and HIV by decreasing cholesterol levels in infected cells. Proc Natl Acad Sci USA. 2010;107(40):17176–17181. doi:10.1073/pnas.1009445107.
  • Liu Y, Wei Z, Ma X, et al. 25-Hydroxycholesterol activates the expression of cholesterol 25-hydroxylase in an LXR-dependent mechanism. J Lipid Res. 2018;59(3):439–451. doi:10.1194/jlr.M080440.
  • Barkas F, Milionis H, Anastasiou G, et al. Statins and PCSK9 inhibitors: What is their role in coronavirus disease 2019? Med Hypotheses. 2021;146:110452. doi:10.1016/j.mehy.2020.
  • Liou J-W, Mani H, Yen J-H. Viral hepatitis, cholesterol metabolism, and cholesterol-lowering natural compounds. Int J Mol Sci. 2022;23(7):3897. doi:10.3390/ijms23073897.

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