Genetic deficiency and polymorphisms of cyclophilin A reveal its essential role for Human Coronavirus 229E replication.

Genetic deficiency and polymorphisms of cyclophilin A reveal its essential role for Human Coronavirus 229E replication.
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DOI:
10.1016/j.coviro.2015.08.004
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发表时间:
2015-10
影响因子:
5.9
通讯作者:
Carbajo-Lozoya J
Carbajo-Lozoya J
中科院分区:
医学2区
文献类型:
--
作者:
von Brunn A;Ciesek S;von Brunn B;Carbajo-Lozoya J

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非免疫抑制衍生物在体外抑制冠状病毒复制。冠状病毒NL63和229E的复制依赖于CypA。编码PPIA基因中的非同义SNP变体限制了HCoV-229E的复制。冠状病毒的复制在体外被环孢菌素A抑制,环孢素A是一种众所周知的免疫抑制药物,它与细胞亲环素结合,从而使其酶促顺-反肽-脯氨基异构酶功能失活。后者是细胞蛋白质和几种病毒蛋白质正确折叠所必需的。在这里,我们总结了目前关于亲环素A在冠状病毒复制中的作用的知识。我们提供了亲环素A单核苷酸多态突变体对人CoV-229E复制的影响的数据,证明了亲环素A正确的功能对病毒繁殖的要求。结果将细胞亲环素A定义为抑制从相对轻微的普通感冒到高致病性SARS-CoV和MERS-CoV病毒的宿主靶标,其观点是揭示非免疫抑制环孢素A类似物广泛灭活冠状病毒家族的观点。
Non-immunosuppressive derivatives inhibit CoV replication in vitro. Coronavirus NL63 and 229E replication depends on CypA. Coding non-synonymous SNP variants in the PPIA gene limit HCoV-229E replication. Replication of coronaviruses is inhibited in vitro by cyclosporin A, a well-known immunosuppressive drug which binds to cellular cyclophilins thus inactivating their enzymatic cis-trans peptidyl-prolyl isomerase function. Latter is required for proper folding of cellular proteins and of proteins of several viruses. Here, we summarize present knowledge on the role of cyclophilin A during coronavirus replication. We present data on the effect of cyclophilin A single nucleotide polymorphism mutants on the replication of human CoV-229E demonstrating the requirement of proper cyclophilin A function for virus propagation. Results define cellular cyclophilin A as a host target for inhibition of coronaviruses ranging from relatively mild common cold to highly pathogenic SARS-CoV and MERS-CoV viruses with the perspective of disclosing non-immunosuppressive cyclosporin A analogs to broadly inactivate the coronavirus family.
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