Department of Immunology & Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Gen Virol. 2010 May;91(Pt 5):1189-93. doi: 10.1099/vir.0.018531-0. Epub 2010 Jan 27.
The mechanisms by which cyclophilin A (CypA) governs hepatitis C virus (HCV) replication remain unknown. Since CypA binds two essential components of the HCV replication complex (RC)--the polymerase NS5B and the phosphoprotein NS5A--we asked in this study whether CypA regulates their RC association. We found that CypA, via its isomerase pocket, locates in a protease-resistant compartment similar to that where HCV replicates. CypA association with this compartment is not mediated by HCV. Moreover, CypA depletion of RC does not influence NS5A and NS5B RC association, arguing against a model where CypA governs HCV replication by recruiting NS5A or NS5B into RC.
亲环素 A (CypA) 调控丙型肝炎病毒 (HCV) 复制的机制尚不清楚。由于 CypA 结合了 HCV 复制复合物 (RC) 的两个必需成分——聚合酶 NS5B 和磷酸蛋白 NS5A——我们在这项研究中询问 CypA 是否调节它们的 RC 结合。我们发现 CypA 通过其异构酶口袋定位于类似于 HCV 复制的蛋白酶抗性隔室。CypA 与该隔室的结合不是由 HCV 介导的。此外，CypA 耗尽 RC 并不影响 NS5A 和 NS5B RC 结合，这排除了 CypA 通过将 NS5A 或 NS5B 募集到 RC 中来调控 HCV 复制的模型。
