Phosphorylation controls the nuclear-cytoplasmic shuttling of influenza A virus nucleoprotein

Journal of Virology
Weinan ZhengWenjun Liu

Abstract

The nucleoprotein (NP) is a major component of the viral ribonucleoprotein (vRNP) complex. During the replication of influenza virus, the vRNP complex undergoes nuclear-cytoplasmic shuttling, during which NP serves as one of the determinants. To date, many phosphorylation sites on NP have been identified, but the biological functions of many of these phosphorylation sites remain unknown. In the present study, the functions of the phosphorylation sites S9, Y10, and Y296 were characterized. These residues are highly conserved, and their phosphorylation was essential for virus growth in cell culture and in a mouse model by regulating the activity of the viral polymerase and the nuclear-cytoplasmic shuttling of NP. The phosphorylation and dephosphorylation of S9 and Y10 controlled nuclear import of NP by affecting the binding affinity between NP and different isoforms of importin-α. In addition, the phosphorylation of Y296 caused nuclear retention of NP by reducing the interaction between NP and CRM1. Furthermore, tyrosine phosphorylation of NP during the early stage of virus infection was ablated when Y296 was mutated to F. However, at later stages of infection, it was weakened by the Y10F mutation. Taken together, the present dat...Continue Reading

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Citations

May 27, 2015·Viruses·Jing LiWenjun Liu
Jun 21, 2016·Viruses·Sebastian GieseMartin Schwemmle
Nov 1, 2016·Evolution; International Journal of Organic Evolution·Claudia BankJeffrey D Jensen
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Dec 8, 2017·Scientific Reports·Alice LabaronneThibaut Crépin
Mar 21, 2018·The Journal of Biological Chemistry·Dai HatakeyamaTakashi Kuzuhara
Sep 8, 2017·Journal of Virology·Takanari GotoSeiji Hongo
Sep 30, 2016·Journal of Virology·James KiruiAndrew Mehle
Aug 24, 2018·Journal of Virology·Bersabeh TigabuAlexander Bukreyev
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Oct 6, 2020·The Journal of General Virology·Yucen LiXin Ye
Jan 20, 2021·Journal of Proteome Research·Paige HaasRuth Hüttenhain
May 24, 2021·Cell Communication and Signaling : CCS·Juane LuHaihua Ruan

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