tetano
Editor, Senior Moderator
J Virol. 2014 Jun 11. pii: JVI.00509-14. [Epub ahead of print]
Sumoylation of influenza A virus nucleoprotein is essential for intracellular trafficking and virus growth.
Han Q1, Chang C1, Li L1, Klenk C2, Cheng J3, Chen Y4, Xia N4, Shu Y5, Chen Z6, Gabriel G7, Sun B8, Xu K9.
Author information
Abstract
Viruses take advantage of host post-translational modifications for their own benefit. It was recently reported that influenza A virus proteins interact extensively with the host sumoylation system. Thereby, several viral proteins, including NS1 and M1, are sumoylated to facilitate viral replication. However, to what extent sumoylation is exploited by influenza A virus is not fully understood. In this study, we found that influenza A virus nucleoprotein (NP) is a bona fide target of sumoylation in both NP-transfected cells and virus-infected cells. We further identified that NP is sumoylated at the two most N-terminal residues, lysine 4 and lysine 7, and that sumoylation at lysine 7 of NP is highly conserved across different influenza A subtypes and strains, including the recently emerged human H7N9 virus. While NP stability and polymerase activity are little affected by sumoylation, the NP-sumoylation-defective virus, WSN-NPK4,7R virus, exhibited an early cytoplasmic localization of NP. The growth of the WSN-NPK4,7R virus was highly attenuated compared to that of WSN-WT virus, and lysine residue at position 7 is indispensable for the virus survival as illustrated by the rapid emergence of revertant viruses. Thus, sumoylation of influenza A virus NP is essential for intracellular trafficking of NP and for virus growth, illustrating sumoylation as a crucial strategy extensively exploited by influenza A virus for survival in the host.
IMPORTANCE:
The host post-translational modifications are heavily targeted by viruses for their own benefits. We and others previously reported that influenza A virus interacts extensively with host sumoylation system. However, the functional outcomes of viral sumoylation are not fully understood. Here we identified that influenza A virus nucleoprotein (NP), a essential component for virus replication, is a new target of SUMO. This is the first report to identify that NP from different influenza A viruses, including the recently emerged H7N9, is sumoylated at the conserve lysine 7. Our data further illustrated that sumoylation of influenza A virus NP is essential for intracellular trafficking of NP and the virus growth, indicating that influenza A virus relies deeply on sumoylation to survive in host cells. Strategies to down-regulate viral sumoylation could thus be a potential anti-viral treatment.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24920808
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24920808
Sumoylation of influenza A virus nucleoprotein is essential for intracellular trafficking and virus growth.
Han Q1, Chang C1, Li L1, Klenk C2, Cheng J3, Chen Y4, Xia N4, Shu Y5, Chen Z6, Gabriel G7, Sun B8, Xu K9.
Author information
Abstract
Viruses take advantage of host post-translational modifications for their own benefit. It was recently reported that influenza A virus proteins interact extensively with the host sumoylation system. Thereby, several viral proteins, including NS1 and M1, are sumoylated to facilitate viral replication. However, to what extent sumoylation is exploited by influenza A virus is not fully understood. In this study, we found that influenza A virus nucleoprotein (NP) is a bona fide target of sumoylation in both NP-transfected cells and virus-infected cells. We further identified that NP is sumoylated at the two most N-terminal residues, lysine 4 and lysine 7, and that sumoylation at lysine 7 of NP is highly conserved across different influenza A subtypes and strains, including the recently emerged human H7N9 virus. While NP stability and polymerase activity are little affected by sumoylation, the NP-sumoylation-defective virus, WSN-NPK4,7R virus, exhibited an early cytoplasmic localization of NP. The growth of the WSN-NPK4,7R virus was highly attenuated compared to that of WSN-WT virus, and lysine residue at position 7 is indispensable for the virus survival as illustrated by the rapid emergence of revertant viruses. Thus, sumoylation of influenza A virus NP is essential for intracellular trafficking of NP and for virus growth, illustrating sumoylation as a crucial strategy extensively exploited by influenza A virus for survival in the host.
IMPORTANCE:
The host post-translational modifications are heavily targeted by viruses for their own benefits. We and others previously reported that influenza A virus interacts extensively with host sumoylation system. However, the functional outcomes of viral sumoylation are not fully understood. Here we identified that influenza A virus nucleoprotein (NP), a essential component for virus replication, is a new target of SUMO. This is the first report to identify that NP from different influenza A viruses, including the recently emerged H7N9, is sumoylated at the conserve lysine 7. Our data further illustrated that sumoylation of influenza A virus NP is essential for intracellular trafficking of NP and the virus growth, indicating that influenza A virus relies deeply on sumoylation to survive in host cells. Strategies to down-regulate viral sumoylation could thus be a potential anti-viral treatment.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24920808
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24920808