Sumoylation of Human Parainfluenza Virus Type 3 Phosphoprotein Correlates with A Reduction in Viral Replication
Sumoylation of Human Parainfluenza Virus Type 3 Phosphoprotein Correlates with A Reduction in Viral Replication
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DOI：
10.1007/s12250-020-00314-2
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发表时间：
2020-11-16
影响因子：
5.5
通讯作者：
Chen, Mingzhou
中科院分区：
文献类型：
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作者：
Cheng, Qi;Huai, Wenjing;Chen, Mingzhou
人类副流感病毒3型（HPIV 3）是副粘病毒科的一个成员，可引起婴幼儿的下呼吸道疾病。HPIV 3的磷蛋白（P）是病毒RNA依赖性RNA聚合酶大蛋白（L）的重要辅因子。P连接核衣壳蛋白（N）和L，启动基因组转录和复制。类小泛素化影响靶蛋白的许多重要途径，并且许多病毒蛋白本身也被类小泛素化。在本研究中，我们发现HPIV 3的P可以被sumoylated，并且K492和K532突变为精氨酸（P-K492 R/K532 R）不能在P内被sumoylated，这增强了HPIV 3小基因组活性。生化研究表明，P-K492 R/K532 R对N的作用、同源四聚体的形成和包涵体的形成均无影响。最后，我们发现将K492 R/K532 R掺入重组HPIV 3（rHPIV 3-P-K492 R/K532 R）中增加了培养细胞中的病毒产量，表明类小泛素化减弱了P的功能并下调了病毒复制。
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 (P-K492R/K532R) failed to be sumoylated within P, which enhances HPIV3 minigenome activity. Biochemical studies showed that P-K492R/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-P-K492R/K532R) increased viral production in culture cells, suggesting that sumoylation attenuates functions of P and down-regulates viral replication.