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Sumoylation of Human Parainfluenza Virus Type 3 Phosphoprotein Correlates with A Reduction in Viral Replication
Virologica Sinica ( IF 4.3 ) Pub Date : 2020-11-16 , DOI: 10.1007/s12250-020-00314-2
Qi Cheng 1 , Wenjing Huai 1 , Xiaoyan Wu 1 , Mingzhou Chen 1
Affiliation  

Human parainfluenza virus type 3 (HPIV3), a member of the Paramyxoviridae family, can cause lower respiratory disease in infants and young children. The phosphoprotein (P) of HPIV3 is an essential cofactor of the viral RNA-dependent RNA polymerase large protein (L). P connects nucleocapsid protein (N) with L to initiate genome transcription and replication. Sumoylation influences many important pathways of the target proteins, and many viral proteins are also themselves sumoylated. In this study, we found that the P of HPIV3 could be sumoylated, and mutation of K492 and K532 to arginine (PK492R/K532R) failed to be sumoylated within P, which enhances HPIV3 minigenome activity. Biochemical studies showed that PK492R/K532R had no effect on its interactions with N, formation of homo-tetramers and formation of inclusion bodies. Finally, we found that incorporation of K492R/K532R into a recombinant HPIV3 (rHPIV3-PK492R/K532R) increased viral production in culture cells, suggesting that sumoylation attenuates functions of P and down-regulates viral replication.



中文翻译:

人类副流感病毒 3 型磷蛋白的 Sumoylation 与病毒复制减少相关

人类副流感病毒 3 型 (HPIV3) 是副粘病毒科的成员,可引起婴儿和幼儿的下呼吸道疾病。HPIV3 的磷蛋白 (P) 是病毒 RNA 依赖性 RNA 聚合酶大蛋白 (L) 的重要辅助因子。P 将核衣壳蛋白 (N) 与 L 连接起来以启动基因组转录和复制。Sumoylation 影响目标蛋白的许多重要途径,许多病毒蛋白本身也被 sumoylated。在本研究中,我们发现HPIV3的P可以被SUMO化,K492和K532突变为精氨酸(P K492R/K532R)在P内未能被SUMO化,这增强了HPIV3的小基因组活性。生化研究表明 P K492R/K532R对它与 N 的相互作用、同四聚体的形成和包涵体的形成没有影响。最后,我们发现将 K492R/K532R 掺入重组 HPIV3 (rHPIV3-P K492R/K532R ) 增加了培养细胞中的病毒产量,表明 sumoylation 减弱了 P 的功能并下调了病毒复制。

更新日期:2020-11-16
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