tetano
Editor, Senior Moderator
J Virol. 2010 Nov 3. [Epub ahead of print]
SUMO1 modification of the non-structural protein 1 of influenza A virus.
Xu K, Klenk C, Liu B, Keiner B, Cheng J, Zheng BJ, Li L, Han Q, Wang C, Li T, Chen Z, Shu Y, Liu J, Klenk HD, Sun B.
Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, 225 South Chongqing Road, Shanghai 200025, China; Institute of Pharmacology and Toxicology, University of W?rzburg, Versbacher Strasse 9, W?rzburg D-97078, Germany; School of Medicine, Shanghai Jiao-Tong University, Shanghai 200025, China; Institute of Virology, Philipps University of Marburg, Hans-Meerwein-Str.2, Marburg 35043, Germany; Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China; Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei, China; Shanghai Institute of Biological Products, Shanghai 200052, China; Chinese Center for Disease Control and Prevention, Yingxin Street 100, Xuanwu District, Beijing 100052, China; Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Abstract
The non-structural protein 1 (NS1 protein) is one of the major factors for efficient infection rate and high virulence of influenza A virus. Although only consisting of approximately 230 amino acids, NS1 has the ability to interfere with several systems of the host viral defense. In the present study, we demonstrate that NS1 of the highly pathogenic avian influenza A/Duck/Hubei/L-1/2004(H5N1) virus interacts with human Ubc9 which is the E2-conjugating enzyme for SUMOylation, and we show that SUMO1 is conjugated to H5N1 NS1 both in transfected and infected cells. Furthermore, two lysine residues in the C-terminus of NS1 were identified as SUMO1 acceptor sites. When the SUMO1 acceptor sites were removed by mutation, NS1 underwent rapid degradation. Studies on different influenza A virus strains of human and avian origin showed that the majority of viruses possess a NS1 protein that is modified by SUMO1, except for the recently emerged swine-origin influenza A virus (S-OIV) H1N1. Interestingly, growth of SUMOylation-deficient WSN virus was retarded when compared to wild type virus. Together, these results indicate that SUMOylation enhances NS1 stability and thus promotes rapid growth of influenza A virus.
PMID: 21047957 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21047957
SUMO1 modification of the non-structural protein 1 of influenza A virus.
Xu K, Klenk C, Liu B, Keiner B, Cheng J, Zheng BJ, Li L, Han Q, Wang C, Li T, Chen Z, Shu Y, Liu J, Klenk HD, Sun B.
Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, 225 South Chongqing Road, Shanghai 200025, China; Institute of Pharmacology and Toxicology, University of W?rzburg, Versbacher Strasse 9, W?rzburg D-97078, Germany; School of Medicine, Shanghai Jiao-Tong University, Shanghai 200025, China; Institute of Virology, Philipps University of Marburg, Hans-Meerwein-Str.2, Marburg 35043, Germany; Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China; Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei, China; Shanghai Institute of Biological Products, Shanghai 200052, China; Chinese Center for Disease Control and Prevention, Yingxin Street 100, Xuanwu District, Beijing 100052, China; Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Abstract
The non-structural protein 1 (NS1 protein) is one of the major factors for efficient infection rate and high virulence of influenza A virus. Although only consisting of approximately 230 amino acids, NS1 has the ability to interfere with several systems of the host viral defense. In the present study, we demonstrate that NS1 of the highly pathogenic avian influenza A/Duck/Hubei/L-1/2004(H5N1) virus interacts with human Ubc9 which is the E2-conjugating enzyme for SUMOylation, and we show that SUMO1 is conjugated to H5N1 NS1 both in transfected and infected cells. Furthermore, two lysine residues in the C-terminus of NS1 were identified as SUMO1 acceptor sites. When the SUMO1 acceptor sites were removed by mutation, NS1 underwent rapid degradation. Studies on different influenza A virus strains of human and avian origin showed that the majority of viruses possess a NS1 protein that is modified by SUMO1, except for the recently emerged swine-origin influenza A virus (S-OIV) H1N1. Interestingly, growth of SUMOylation-deficient WSN virus was retarded when compared to wild type virus. Together, these results indicate that SUMOylation enhances NS1 stability and thus promotes rapid growth of influenza A virus.
PMID: 21047957 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21047957