國家衛生研究院 NHRI:Item 3990099045/12463

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Title:	Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation
Authors:	Hung, SJ;Hsu, YM;Huang, SW;Tsai, HP;Lee, LYY;Hurt, AC;Barr, IG;Shih, SR;Wang, JR
Contributors:	National Institute of Infectious Diseases and Vaccinology;National Mosquito-Borne Diseases Control Research Center
Abstract:	BACKGROUND: Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. METHODS: To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties. RESULTS: The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo. CONCLUSIONS: These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention.
Date:	2020-01-06
Relation:	Journal of Biomedical Science. 2020 Jan 6;27(1):Article number 17.
Link to:	http://dx.doi.org/10.1186/s12929-019-0612-z
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1021-7770&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000513508300001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85077631393
Appears in Collections:	[Others] Periodical Articles [Sheng-Wen Huang] Periodical Articles

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