Title Identification and Characterization of Three Novel Nuclear Export Signals in the Influenza A Virus Nucleoprotein
Authors Yu, Maorong
Liu, Xiaoling
Cao, Shuai
Zhao, Zhendong
Zhang, Ke
Xie, Qing
Chen, Caiwei
Gao, Shengyan
Bi, Yuhai
Sun, Lei
Ye, Xin
Gao, George F.
Liu, Wenjun
Affiliation Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China.
Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China.
Chinese Acad Sci, Grad Univ, Beijing, Peoples R China.
Chinese Acad Sci, Inst Microbiol, China Japan Joint Lab Mol Immunol & Mol Microbiol, Beijing, Peoples R China.
Keywords MESSENGER-RNAS
RIBONUCLEOPROTEIN COMPLEXES
LOCALIZATION SEQUENCES
MUTATIONAL ANALYSIS
PROTEIN
REPLICATION
BINDING
IMPORT
ALPHA
CELLS
Issue Date 2012
Publisher 病毒学杂志
Citation JOURNAL OF VIROLOGY.2012,86,(9),4970-4980.
Abstract The nuclear export of the influenza A virus ribonucleoprotein (vRNP) is crucial for virus replication. As a major component of the vRNP, nucleoprotein (NP) alone can also be shuttled out of the nucleus by interacting with chromosome region maintenance 1 (CRM1) and is therefore hypothesized to promote the nuclear export of the vRNP. In the present study, three novel nuclear export signals (NESs) of the NP-NES1, NES2, and NES3-were identified as being responsible for mediating its nuclear export. The nuclear export of NES3 was CRM1 dependent, whereas that of NES1 or NES2 was CRM1 independent. Inactivation of these NESs led to an overall nuclear accumulation of NP. Mutation of all three NP-NESs significantly impaired viral replication. Based on structures of influenza virus NP oligomers, these three hydrophobic NESs are found present on the surface of oligomeric NPs. Functional studies indicated that oligomerization is also required for nuclear export of NP. Together, these results suggest that the nuclear export of NP is important for virus replication and relies on its NESs and oligomerization.
URI http://hdl.handle.net/20.500.11897/323229
ISSN 0022-538X
DOI 10.1128/JVI.06159-11
Indexed SCI(E)
Appears in Collections: 药学院
天然药物与仿生药物国家重点实验室

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