Nucleoprotein phosphorylation site(Y385)mutation confers temperature sensitivity to influenza A virus due to impaired nucleoprotein oligomerization at a lower temperature  

作　　者：Weinan Zheng Liang Cui Minghui Li Yun Li Wenhui Fan Limin Yang Jing Li Lei Sun Wenjun Liu 

机构地区：[1]CAS Key Laboralory of Pathogenic Microbiology and Immumology,Institute of Microbiology,Chinese Academy of Sciences,Bejing 100101,China [2]University of Chinese Academy of Sciences,Bejing 100101,China [3]State Key Laboratory for Conservation and Urilization of Subtropical Agro-Bioresourses&Laboratory of Animal Infectious Diseases,College of Animal Sciences and Veterinary Medicine,Guangxi Universit,Nanning 530004,China [4]Instinute of Microbiology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Beijing 100101,China

出　　处：《Science China(Life Sciences)》2021年第4期633-643,共11页中国科学（生命科学英文版）

基　　金：supported by grants from the Strategic Priority Research Program of Chinese Academy of Sciences(XDB29010000);the National Natural Science Foundation of China(31630079,31972657,31672531);the National Key Research and Development Program of China(2016YFD0500206);the Mega-Project of Guangxi Natural Science Foundation(2015GXNSFEA139002);supported by Youth Innovation Promotion Association of CAS(2019091)。

摘　　要：Mutations in viral proteins can lead to the cold adaption of influenza A virus and the cold-adapted virus is an important vaccination instrument.Here,we identify a novel strain of influenza A virus with cold sensitivity conferred by a mutation at a phosphorylation site within the nucleoprotein(NP).The highly conserved tyrosine 385 residue(Y385)of NP was identified as a phosphorylation site by mass spectrometry.The constructive NP phosphorylation mimicked by Y385 E mutation was fatal for virus replication,while the continuous Y385 dephosphorylation mimicked by Y385 F mutation had little impact on virus replication in vitro.Notably,the Y385 F virus showed much lower replicative capacity in turbinates of mice compared with the wild type virus.Moreover,the replication of Y385 F virus was significantly reduced in both A549 and MDCK cells grown at 33℃,when compared to that at 37℃.These results indicated that the Y385 F mutation led to cold sensitivity of virus.We further found that the cold sensitivity of Y385 F virus could be attributed to diminished NP oligomerization rather than any changes in intracellular localization.Taken together,these findings suggest that the phosphorylation of NP may be a critical factor that regulates the temperature sensitivity of influenza A virus.

关 键 词：influenza A virus NUCLEOPROTEIN PHOSPHORYLATION DEPHOSPHORYLATION temperature sensitivity 

分 类 号：R373.13[医药卫生—病原生物学]