Chaperonin CCT5 binding with porcine parvovirus NS1 promotes the interaction of NS1 and COPƐ to facilitate viral replication
Chaperonin CCT5 binding with porcine parvovirus NS1 promotes the interaction of NS1 and COPƐ to facilitate viral replication
复制标题
伴侣蛋白 CCT5 与猪细小病毒 NS1 结合促进 NS1 和 COPÆ 相互作用，促进病毒复制
DOI：
10.1016/j.vetmic.2022.109574
复制
发表时间：
2022
影响因子：
3.3
通讯作者：
Dewen Tong
中科院分区：
文献类型：
--
作者：
Qian Du;Xuezhi Zhang;Ning Xu;Mengyu Ma;Bicheng Miao;Yong Huang;Dewen Tong
猪细小病毒（Porcine parvovirus，PPV）是引起初孕母猪繁殖障碍的重要病原。猪细小病毒非结构蛋白NS 1是一种多功能蛋白，在病毒复制过程中起关键作用。含伴侣蛋白的T复合多肽复合物（CCT）是一类与蛋白质相互作用的II型伴侣蛋白，含有CCT 1-CCT 8亚基，有助于蛋白质的折叠和维持。本研究首次发现CCT 5是PPV NS 1的宿主相互作用蛋白之一，并且CCT 5与NS 1直接结合。通过特异性siRNA干扰CCT 5表达和通过CRISPR/Cas9敲除CCT 5表达抑制PPV复制，而过表达CCT 5促进PK-15细胞中PPV复制。CCT 5与PPV NS 1的相互作用依赖于NS 1 N-末端的36-42 aa基序。更重要的是，还发现CCT 5与COP 3相互作用，COP 3先前已被证明通过调节I型干扰素促进PPV复制。干扰和敲除CCT 5基因的表达可显著降低PPV NS 1与宿主蛋白COP 3的相互作用，促进IFN-β的表达。这些结果表明，CCT 5介导PPV NS 1和COP 3的相互作用来调节病毒复制，为PPV复制机制提供了新的见解。·CCT 5是与PPV NS 1直接结合的宿主蛋白之一。·CCT 5参与PPV复制的调节。PPV NS 1和CCT 5的相互作用取决于NS 1 N-末端的36-42 aa基序。·CCT 5决定PPV NS 1和调节病毒复制的宿主蛋白COP 3的相互作用。
Porcine parvovirus (PPV) is an important pathogen causing reproductive disorders in first pregnant sows. The non-structure protein NS1 of PPV is a multifunctional protein playing a key role in viral replication. Chaperonin-containing T-complex polypeptide complex (CCT), containing CCT1-CCT8 subunits, belongs to the type II chaperones that interact with proteins to help in folding and maintaining. In this study, CCT5, for the first time, was found to be one of the host interacting proteins of PPV NS1, and CCT5 was directly bound with NS1. Interference of CCT5 expression by specific siRNA and knockout of CCT5 expression by CRISPR/Cas9 suppressed PPV replication, while overexpression of CCT5 promoted PPV replication in PK-15 cells. The interaction of CCT5 and PPV NS1 was dependent on the 36-42 aa motif at the N-terminal end of NS1. More importantly, CCT5 was also found interacting with COPƐ, which has previously been demonstrated to promote PPV replication by regulating type I interferon. Interference and knockout of CCT5 expression significantly reduced the interaction of PPV NS1 and host protein COPƐ, and promoted the IFN-β expression. These results show that CCT5 mediates the interaction of PPV NS1 and COPƐ to regulate viral replication, providing new insight into the mechanism of PPV replication. • CCT5 is one of the host proteins directly binding with PPV NS1. • CCT5 participates in the regulation of PPV replication. • The interaction of PPV NS1 and CCT5 depends on the 36-42 aa motif at the N-terminal end of NS1. • CCT5 determines the interaction of PPV NS1 and host protein COPƐ that regulates viral replication.