Cheng Jun-Jun, Li Jian-Rui, Huang Meng-Hao, Ma Lin-Lin, Wu Zhou-Yi, Jiang Chen-Chen, Li Wen-Jing, Li Yu-Huan, Han Yan-Xing, Li Hu, Chen Jin-Hua, Wang Yan-Xiang, Song Dan-Qing, Peng Zong-Gen, Jiang Jian-Dong
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.
Sci Rep. 2016 Feb 22;6:21808. doi: 10.1038/srep21808.
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.
分化簇36（CD36）是一种与脂质代谢相关的膜蛋白。我们发现，体外丙型肝炎病毒（HCV）感染可增加表面形式或可溶性形式的CD36表达。CD36与HCV E1蛋白之间的直接相互作用促进了HCV的附着，导致其进入和复制增强。CD36的HCV共受体作用独立于清道夫受体BI（SR-BI）。CD36单克隆抗体可中和CD36的作用并减少HCV复制。CD36抑制剂磺基-N-琥珀酰亚胺油酸酯（SSO）直接结合CD36而非SR-BI，可显著阻断HCV进入，从而抑制HCV复制。SSO的抗病毒作用仅见于HCV，而不见于其他病毒。SSO与已知的抗HCV药物联合使用对HCV表现出额外的抑制作用。SSO在小鼠中相当安全。总之，CD36与HCV E1相互作用，可能是HCV进入所特有的共受体；因此，CD36可能是抗HCV的潜在药物靶点。
