PMID- 24741105
OWN - NLM
STAT- MEDLINE
DCOM- 20150120
LR  - 20231213
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 88
IP  - 13
DP  - 2014 Jul
TI  - Characteristics of nucleocytoplasmic transport of H1N1 influenza A virus nuclear 
      export protein.
PG  - 7455-63
LID - 10.1128/JVI.00257-14 [doi]
AB  - The influenza A virus nuclear export protein (NEP) plays crucial roles in the 
      nuclear export of the viral ribonucleoprotein complex through the chromosome 
      region maintenance 1 (CRM1)-mediated cellular protein transport system. However, 
      the detailed mechanism of NEP nucleocytoplasmic trafficking remains incompletely 
      understood. Here, we investigated the subcellular localization of NEP from two 
      strains of H1N1 influenza A virus and found that 2009 swine-origin H1N1 influenza 
      A virus A/California/04/2009 (CA04) NEP displayed a distinct cellular 
      distribution pattern, forming unique nuclear aggregates, compared to A/WSN/33 
      (H1N1) (WSN) NEP. Characterization of the nucleocytoplasmic transport pathways of 
      these two NEPs showed that they both enter the nucleus by passive diffusion but 
      are exported through the nuclear export receptor CRM1-mediated pathway with 
      different efficiencies. The two identified nuclear export signals (NESs) on the 
      two NEPs functioned similarly despite differences in their amino acid sequences. 
      Using a two-hybrid assay, we confirmed that the CA04 NEP interacts less 
      efficiently with CRM1 and that a threonine residue at position 48 is responsible 
      for the nuclear aggregation. The present study revealed the dissimilarity in 
      subcellular NEP transport processes between the 2009 pandemic (H1N1) influenza A 
      virus CA04 and the laboratory-adapted H1N1 virus WSN and uncovered the mechanism 
      responsible for this difference. IMPORTANCE: Because the efficiency of the 
      nucleocytoplasmic transport of viral components is often correlated with the 
      viral RNA polymerase activity, propagation, and host range of influenza viruses, 
      the present study investigated the subcellular localization of NEP from two 
      strains of H1N1 influenza virus. We found that the NEPs of both 
      A/California/04/2009 (H1N1) (CA04) and A/WSN/33 (H1N1) (WSN) enter the nucleus by 
      passive diffusion but are exported with different efficiencies, which were caused 
      by weaker binding activity between the CA04 NEP and CRM1. The results of the 
      present study revealed characteristics of the nuclear import and export pathways 
      of NEP and the mechanism responsible for the differences in the cellular 
      distribution of NEP between two H1N1 strains.
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Gao, Shengyan
AU  - Gao S
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Beijing, China University of Chinese 
      Academy of Sciences, Beijing, China.
FAU - Wang, Shanshan
AU  - Wang S
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Beijing, China University of Chinese 
      Academy of Sciences, Beijing, China.
FAU - Cao, Shuai
AU  - Cao S
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Beijing, China.
FAU - Sun, Lei
AU  - Sun L
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Beijing, China.
FAU - Li, Jing
AU  - Li J
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Beijing, China.
FAU - Bi, Yuhai
AU  - Bi Y
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Beijing, China.
FAU - Gao, George F
AU  - Gao GF
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Beijing, China.
FAU - Liu, Wenjun
AU  - Liu W
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Beijing, China liuwj@im.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140416
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Karyopherins)
RN  - 0 (Nuclear Export Signals)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
SB  - IM
MH  - Active Transport, Cell Nucleus/*physiology
MH  - Cell Nucleus/metabolism
MH  - Humans
MH  - Influenza A Virus, H1N1 Subtype/classification/*physiology
MH  - Influenza, Human/*metabolism/virology
MH  - Karyopherins/*metabolism
MH  - Microscopy, Fluorescence
MH  - Nuclear Export Signals/*physiology
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
MH  - Subcellular Fractions
MH  - Two-Hybrid System Techniques
MH  - Virus Replication/physiology
MH  - Exportin 1 Protein
PMC - PMC4054460
EDAT- 2014/04/18 06:00
MHDA- 2015/01/21 06:00
PMCR- 2015/01/01
CRDT- 2014/04/18 06:00
PHST- 2014/04/18 06:00 [entrez]
PHST- 2014/04/18 06:00 [pubmed]
PHST- 2015/01/21 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - JVI.00257-14 [pii]
AID - 00257-14 [pii]
AID - 10.1128/JVI.00257-14 [doi]
PST - ppublish
SO  - J Virol. 2014 Jul;88(13):7455-63. doi: 10.1128/JVI.00257-14. Epub 2014 Apr 16.