The Nuclear Export Protein of H5N1 Influenza A Viruses Recruits Matrix 1 (M1) Protein to the Viral Ribonucleoprotein to Mediate Nuclear Export

被引:61
作者
Brunotte, Linda [1 ]
Flies, Joe [1 ]
Bolte, Hardin [1 ]
Reuther, Peter [1 ]
Vreede, Frank [2 ]
Schwemmle, Martin [1 ]
机构
[1] Univ Med Ctr Freiburg, Inst Virol, D-79104 Freiburg, Germany
[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX 3RE, England
关键词
NS2; PROTEIN; CYTOPLASMIC TRANSPORT; ADAPTIVE MUTATIONS; RNA; BINDING; REPLICATION; MEMBRANE; SIGNAL; IDENTIFICATION; INTERMEDIATE;
D O I
10.1074/jbc.M114.569178
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In influenza A virus-infected cells, replication and transcription of the viral genome occurs in the nucleus. To be packaged into viral particles at the plasma membrane, encapsidated viral genomes must be exported from the nucleus. Intriguingly, the nuclear export protein (NEP) is involved in both processes. Although NEP stimulates viral RNA synthesis by binding to the viral polymerase, its function during nuclear export implicates interaction with viral ribonucleoprotein (vRNP)-associated M1. The observation that both interactions are mediated by the C-terminal moiety of NEP raised the question whether these two features of NEP are linked functionally. Here we provide evidence that the interaction between M1 and the vRNP depends on the NEP C terminus and its polymerase activity-enhancing property for the nuclear export of vRNPs. This suggests that these features of NEP are linked functionally. Furthermore, our data suggest that the N-terminal domain of NEP interferes with the stability of the vRNP-M1-NEP nuclear export complex, probably mediated by its highly flexible intramolecular interaction with the NEP C terminus. On the basis of our data, we propose a new model for the assembly of the nuclear export complex of Influenza A vRNPs.
引用
收藏
页码:20067 / 20077
页数:11
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