Cyclophilin A Inhibits Human Respiratory Syncytial Virus (RSV) Replication by Binding to RSV-N through Its PPIase Activity.
Cyclophilin A Inhibits Human Respiratory Syncytial Virus (RSV) Replication by Binding to RSV-N through Its PPIase Activity.
复制标题
亲环蛋白 A 通过其 PPI 酶活性与 RSV-N 结合，抑制人呼吸道合胞病毒 (RSV) 复制
DOI：
10.1128/jvi.00563-21
复制
发表时间：
2021-07-12
影响因子：
5.4
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Liang W;Zhang Y;Li M;Al-Shaebi F;Li J;Zhang J;Wei L
RSV-N在病毒基因组中形成核糖核蛋白（RNP）复合物，其被RSV RNA依赖性RNA聚合酶（RdRp）复合物识别以启动病毒复制和转录，在病毒生物合成过程中起着不可或缺的作用。与RSV-N结合的cypA可能通过削弱RSV-N和RSV-P之间的相互作用而损害这种功能，从而导致病毒产量降低。我们的研究为cypA的抗病毒功能提供了新的见解，包括与病毒衣壳蛋白结合以抑制病毒复制，这可能有助于新的抗病毒药物的探索。摘要人呼吸道合胞病毒（hRSV）是引起婴幼儿急性下呼吸道感染（ALRI）的最常见病原体。近年来，病毒与宿主的相互作用已成为病毒相关研究的热点，对于RSV感染的研究有待进一步阐述。在这项研究中，我们发现RSV感染显着增加亲环素A（cypA）在临床患者，小鼠和上皮细胞的表达。因此，我们评估了cypA在RSV复制中的功能，并证明了在cypA敲低的宿主细胞中病毒增殖加速，但在cypA过表达的宿主细胞中受到抑制。此外，我们证明了cypA限制RSV复制依赖于其PPIase活性。此外，我们进行了液相色谱-质谱分析，结果表明cypA可以与几种病毒蛋白，如RSV-N，RSV-P和RSV-M2-1相互作用。最后，通过免疫共沉淀和免疫荧光法证实了cypA与RSV-N之间的相互作用。这些结果提供了强有力的证据，cypA可能通过其PPIase活性与RSV-N相互作用而在RSV复制中发挥抑制作用。重要性RSV-N包装在病毒基因组中形成核糖核蛋白（RNP）复合物，由RSV RNA依赖性RNA聚合酶（RdRp）复合物识别，启动病毒复制和转录，在病毒生物合成过程中发挥不可或缺的作用。与RSV-N结合的cypA可能通过削弱RSV-N和RSV-P之间的相互作用而损害这种功能，从而导致病毒产量降低。我们的研究为cypA的抗病毒功能提供了新的见解，包括与病毒衣壳蛋白结合以抑制病毒复制，这可能有助于新的抗病毒药物的探索。
RSV-N, packed in the viral genome to form the ribonucleoprotein (RNP) complex, which is recognized by the RSV RNA-dependent RNA polymerase (RdRp) complex to initiate viral replication and transcription, plays an indispensable role in the viral biosynthesis process. cypA, binding to RSV-N, may impair this function by weakening the interaction between RSV-N and RSV-P, thus leading to decreased viral production. Our research provides novel insight into cypA antiviral function, including binding to viral capsid protein to inhibit viral replication, which may be helpful for new antiviral drug exploration. ABSTRACT Human respiratory syncytial virus (hRSV) is the most common pathogen which causes acute lower respiratory infection (ALRI) in infants. Recently, virus-host interaction has become a hot spot of virus-related research, and it needs to be further elaborated for RSV infection. In this study, we found that RSV infection significantly increased the expression of cyclophilin A (cypA) in clinical patients, mice, and epithelial cells. Therefore, we evaluated the function of cypA in RSV replication and demonstrated that virus proliferation was accelerated in cypA knockdown host cells but restrained in cypA-overexpressing host cells. Furthermore, we proved that cypA limited RSV replication depending on its PPIase activity. Moreover, we performed liquid chromatography-mass spectrometry, and the results showed that cypA could interact with several viral proteins, such as RSV-N, RSV-P, and RSV-M2-1. Finally, the interaction between cypA and RSV-N was certified by coimmunoprecipitation and immunofluorescence. Those results provided strong evidence that cypA may play an inhibitory role in RSV replication through interaction with RSV-N via its PPIase activity. IMPORTANCE RSV-N, packed in the viral genome to form the ribonucleoprotein (RNP) complex, which is recognized by the RSV RNA-dependent RNA polymerase (RdRp) complex to initiate viral replication and transcription, plays an indispensable role in the viral biosynthesis process. cypA, binding to RSV-N, may impair this function by weakening the interaction between RSV-N and RSV-P, thus leading to decreased viral production. Our research provides novel insight into cypA antiviral function, including binding to viral capsid protein to inhibit viral replication, which may be helpful for new antiviral drug exploration.