| 论文题目: | Phosphorylation controls the nuclear-cytoplasmic shuttling of influenza A virus nucleoprotein |
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| 作者: | Weinan Zheng, Jing Li, Shanshan Wang, Shuaishuai Cao, Jingwen Jiang, Can Chen, Chan Ding, Chuan Qin, Xin Ye, F Gao George, and Wenjun* Liu. |
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| 刊物名称: | J Virol |
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| 年份: | 2015 |
| 影响因子: | 4.855 |
| 论文下载: | 下载地址 |
| 摘要: | 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 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 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-alpha. 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 data indicate that the phosphorylation and dephosphorylation of NP control the shuttling of NP between the nucleus and cytoplasm during virus replication. IMPORTANCE: It is well known that phosphorylation regulates the functions of viral proteins and the life cycle of influenza A virus. As the most abundant protein in the vRNP complex of influenza A virus, several phosphorylation sites on NP were identified. However, the functions of these phosphorylation sites were unknown. The present study demonstrated that the phosphorylation status of these sites on NP can mediate its nuclear-cytoplasmic shuttling, which drives the trafficking of vRNP complexes in infected cells. The present data suggest that the phosphorylated residues of NP are multi-step controllers for the virus life cycle and new targets for designing anti-flu drugs. |
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