title: CD36 is a co-receptor for hepatitis C virus E1 protein attachment.
abstract: The cluster of differentiation 36 (CD36) is a membrane protein related to lipid metabolism. We show that HCV infection in vitro increased CD36 expression in either surface or soluble form. HCV attachment was facilitated through a direct interaction between CD36 and HCV E1 protein, causing enhanced entry and replication. The HCV co-receptor effect of CD36 was independent of that of SR-BI. CD36 monoclonal antibodies neutralized the effect of CD36 and reduced HCV replication. CD36 inhibitor sulfo-N-succinimidyl oleate (SSO), which directly bound CD36 but not SR-BI, significantly interrupted HCV entry, and therefore inhibited HCV replication. SSO's antiviral effect was seen only in HCV but not in other viruses. SSO in combination with known anti-HCV drugs showed additional inhibition against HCV. SSO was considerably safe in mice. Conclusively, CD36 interacts with HCV E1 and might be a co-receptor specific for HCV entry; thus, CD36 could be a potential drug target against HCV.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.|State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Cheng
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Jian-Rui
authors.initials: JR
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Meng-Hao
authors.initials: MH
authors.lastname: Huang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Ma
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Zhou-Yi
authors.initials: ZY
authors.lastname: Wu
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Jiang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Yan-Xing
authors.initials: YX
authors.lastname: Han
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Yan-Xiang
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Song
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Zong-Gen
authors.initials: ZG
authors.lastname: Peng
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.|State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100050, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D018955:CD36 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D009829:Oleic Acids / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013388:Succinimides / Q000494:pharmacology*; D023382:Toxicity Tests, Acute; D019076:Transgenes; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D053585:Virus Attachment / Q000187:drug effects*; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D018955:CD36 Antigens; C087035:E1 protein, Hepatitis C virus; D009829:Oleic Acids; D009842:Oligopeptides; D034741:RNA, Small Interfering; D011991:Receptors, Virus; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D013388:Succinimides; D014759:Viral Envelope Proteins; C120556:sulfo-N-succinimidyl oleate; C486464:telaprevir