Phosphorylation and dephosphorylation of threonine 188 in nucleoprotein is crucial for the replication of influenza A virus

Yun Li; Lei Sun; Weinan Zheng; Madina Mahesutihan; Jing Li; Yuhai Bi; Heran Wang; Wenjun Liu; Ting Rong Luo

doi:10.1016/j.virol.2018.05.002

Phosphorylation and dephosphorylation of threonine 188 in nucleoprotein is crucial for the replication of influenza A virus

Virology. 2018 Jul:520:30-38. doi: 10.1016/j.virol.2018.05.002. Epub 2018 May 16.

Authors

Yun Li¹, Lei Sun², Weinan Zheng³, Madina Mahesutihan⁴, Jing Li⁴, Yuhai Bi³, Heran Wang⁵, Wenjun Liu⁶, Ting Rong Luo⁷

Affiliations

¹ State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresourses & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, Guangxi, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
² CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: sunlei362@im.ac.cn.
³ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
⁴ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ International Department, Beijing National Day School, Beijing 100039, China.
⁶ State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresourses & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, Guangxi, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: liuwj@im.ac.cn.
⁷ State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresourses & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, Guangxi, China. Electronic address: tingrongluo@gxu.edu.cn.

PMID: 29775781
DOI: 10.1016/j.virol.2018.05.002

Abstract

Nucleoprotein (NP) is a major component of the viral ribonucleoprotein (vRNP) complex that is responsible for viral replication, transcription and packaging of influenza A virus. Phosphorylation of NP plays an important role during viral infection. In the present study, we identified threonine 188 (T188) as a novel phosphorylated residue in the NP of influenza A virus by using mass spectrometry. T188 is located within nuclear export signal 2 (NES2) which is chromosome region maintenance 1 (CRM1)-independent. We observed that the phosphorylation and dephosphorylation of residue T188 regulated viral replication by controlling NES2-dependent NP nuclear export and the polymerase activity of the vRNP complex. Our findings provide further insights for understanding the replication of influenza A virus.

Keywords: Influenza A virus; Nucleoprotein; Phosphorylation; Viral replication.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Active Transport, Cell Nucleus
Animals
Dogs
Exportin 1 Protein
HEK293 Cells
Host-Pathogen Interactions
Humans
Influenza A virus / enzymology
Influenza A virus / genetics
Influenza A virus / physiology*
Karyopherins / metabolism
Madin Darby Canine Kidney Cells
Mass Spectrometry
Nuclear Export Signals
Nucleocapsid Proteins
Phosphorylation
Protein Binding
RNA-Binding Proteins / chemistry
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism*
Receptors, Cytoplasmic and Nuclear / metabolism
Threonine / chemistry
Threonine / metabolism*
Viral Core Proteins / chemistry
Viral Core Proteins / genetics
Viral Core Proteins / metabolism*
Virus Replication* / genetics

Substances

Karyopherins
NP protein, Influenza A virus
Nuclear Export Signals
Nucleocapsid Proteins
RNA-Binding Proteins
Receptors, Cytoplasmic and Nuclear
Viral Core Proteins
Threonine