Lott W B, Takyar S S, Tuppen J, Crawford D H, Harrison M, Sloots T P, Gowans E J
Clinical Medical Virology Research Centre, University of Queensland, St. Lucia, Queensland 4067, Australia.
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4916-21. doi: 10.1073/pnas.081072798. Epub 2001 Apr 10.
Cobalamins are stored in high concentrations in the human liver and thus are available to participate in the regulation of hepatotropic virus functions. We show that cyanocobalamin (vitamin B12) inhibited the HCV internal ribosome entry site (IRES)-dependent translation of a reporter gene in vitro in a dose-dependent manner without significantly affecting the cap-dependent mechanism. Vitamin B12 failed to inhibit translation by IRES elements from encephalomyocarditis virus (EMCV) or classical swine fever virus (CSFV). We also demonstrate a relationship between the total cobalamin concentration in human sera and HCV viral load (a measure of viral replication in the host). The mean viral load was two orders of magnitude greater when the serum cobalamin concentration was above 200 pM (P < 0.003), suggesting that the total cobalamin concentration in an HCV-infected liver is biologically significant in HCV replication.
钴胺素在人体肝脏中高浓度储存,因此可参与调节嗜肝病毒功能。我们发现,氰钴胺素(维生素B12)在体外以剂量依赖方式抑制报告基因的丙型肝炎病毒(HCV)内部核糖体进入位点(IRES)依赖性翻译,而对帽依赖性机制无显著影响。维生素B12未能抑制脑心肌炎病毒(EMCV)或经典猪瘟病毒(CSFV)的IRES元件介导的翻译。我们还证明了人血清中总钴胺素浓度与HCV病毒载量(宿主中病毒复制的一种衡量指标)之间的关系。当血清钴胺素浓度高于200 pM时,平均病毒载量高两个数量级(P < 0.003),这表明HCV感染肝脏中的总钴胺素浓度在HCV复制中具有生物学意义。