PMID- 23115280 OWN - NLM STAT- MEDLINE DCOM- 20130225 LR - 20211021 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 87 IP - 2 DP - 2013 Jan TI - A second CRM1-dependent nuclear export signal in the influenza A virus NS2 protein contributes to the nuclear export of viral ribonucleoproteins. PG - 767-78 LID - 10.1128/JVI.06519-11 [doi] AB - Influenza A virus NS2 protein, also called nuclear export protein (NEP), is crucial for the nuclear export of viral ribonucleoproteins. However, the molecular mechanisms of NEP mediation in this process remain incompletely understood. A leucine-rich nuclear export signal (NES2) in NEP, located at the predicted N2 helix of the N-terminal domain, was identified in the present study. NES2 was demonstrated to be a transferable NES, with its nuclear export activity depending on the nuclear export receptor chromosome region maintenance 1 (CRM1)-mediated pathway. The interaction between NEP and CRM1 is coordinately regulated by both the previously reported NES (NES1) and now the new NES2. Deletion of the NES1 enhances the interaction between NEP and CRM1, and deletion of the NES1 and NES2 motifs completely abolishes this interaction. Moreover, NES2 interacts with CRM1 in the mammalian two-hybrid system. Mutant viruses containing NES2 alterations generated by reversed genetics exhibit reduced viral growth and delay in the nuclear export of viral ribonucleoproteins (vRNPs). The NES2 motif is highly conserved in the influenza A and B viruses. The results demonstrate that leucine-rich NES2 is involved in the nuclear export of vRNPs and contributes to the understanding of nucleocytoplasmic transport of influenza virus vRNPs. FAU - Huang, Shengping AU - Huang S AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. FAU - Chen, Jingjing AU - Chen J FAU - Chen, Quanjiao AU - Chen Q FAU - Wang, Huadong AU - Wang H FAU - Yao, Yanfeng AU - Yao Y FAU - Chen, Jianjun AU - Chen J FAU - Chen, Ze AU - Chen Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121031 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (NS2 protein, influenza virus A) RN - 0 (Nuclear Export Signals) RN - 0 (Ribonucleoproteins) RN - 0 (Viral Nonstructural Proteins) SB - IM MH - *Active Transport, Cell Nucleus MH - Cell Line MH - Conserved Sequence MH - Humans MH - Influenza A virus/genetics/*physiology MH - *Nuclear Export Signals MH - Protein Binding MH - Protein Interaction Mapping MH - Ribonucleoproteins/*metabolism MH - Sequence Deletion MH - Two-Hybrid System Techniques MH - Viral Nonstructural Proteins/genetics/*metabolism MH - *Virus Replication PMC - PMC3554077 EDAT- 2012/11/02 06:00 MHDA- 2013/02/26 06:00 PMCR- 2013/07/01 CRDT- 2012/11/02 06:00 PHST- 2012/11/02 06:00 [entrez] PHST- 2012/11/02 06:00 [pubmed] PHST- 2013/02/26 06:00 [medline] PHST- 2013/07/01 00:00 [pmc-release] AID - JVI.06519-11 [pii] AID - 06519-11 [pii] AID - 10.1128/JVI.06519-11 [doi] PST - ppublish SO - J Virol. 2013 Jan;87(2):767-78. doi: 10.1128/JVI.06519-11. Epub 2012 Oct 31.