tetano
Editor, Senior Moderator
Plos Pathogens
Shinya Yamada1, Masato Hatta2, Bart L. Staker3,4, Shinji Watanabe2, Masaki Imai2, Kyoko Shinya5, Yuko Sakai-Tagawa1, Mutsumi Ito1, Makoto Ozawa2,6, Tokiko Watanabe2, Saori Sakabe1,7, Chengjun Li2, Jin Hyun Kim2, Peter J. Myler4,8,9, Isabelle Phan4,8, Amy Raymond3,4, Eric Smith3,4, Robin Stacy4,8, Chairul A. Nidom10,11, Simon M. Lank12, Roger W. Wiseman12, Benjamin N. Bimber12, David H. O'Connor12,13, Gabriele Neumann2, Lance J. Stewart3,4*, Yoshihiro Kawaoka1,2,5,6,7,14*
1 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan, 2 Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 3 Emerald BioStructures, Inc., Bainbridge Island, Washington, United States of America, 4 Seattle Structural Genomics Center for Infectious Disease, Washington, United States of America, 5 Department of Microbiology and Infectious Diseases, Kobe University, Hyogo, Japan, 6 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan, 7 ERATO Infection-Induced Host Responses Project, Saitama, Japan, 8 Seattle Biomedical Research Institute, Seattle, Washington, United States of America, 9 Departments of Global Health and Medical Education & Biomedical Informatics, University of Washington, Seattle, Washington, United States of America, 10 Faculty of Veterinary Medicine, Tropical Disease Centre, Airlangga University, Surabaya, Indonesia, 11 Collaborating Research Center-Emerging and Reemerging Infectious Diseases, Tropical Disease Centre, Airlangga University, Surabaya, Indonesia, 12 Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 13 Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 14 Creative Research Initiative, Sousei, Hokkaido University, Sapporo, Japan
Abstract Top
Two amino acids (lysine at position 627 or asparagine at position 701) in the polymerase subunit PB2 protein are considered critical for the adaptation of avian influenza A viruses to mammals. However, the recently emerged pandemic H1N1 viruses lack these amino acids. Here, we report that a basic amino acid at position 591 of PB2 can compensate for the lack of lysine at position 627 and confers efficient viral replication to pandemic H1N1 viruses in mammals. Moreover, a basic amino acid at position 591 of PB2 substantially increased the lethality of an avian H5N1 virus in mice. We also present the X-ray crystallographic structure of the C-terminus of a pandemic H1N1 virus PB2 protein. Arginine at position 591 fills the cleft found in H5N1 PB2 proteins in this area, resulting in differences in surface shape and charge for H1N1 PB2 proteins. These differences may affect the protein's interaction with viral and/or cellular factors, and hence its ability to support virus replication in mammals.
full article
http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1001034
Shinya Yamada1, Masato Hatta2, Bart L. Staker3,4, Shinji Watanabe2, Masaki Imai2, Kyoko Shinya5, Yuko Sakai-Tagawa1, Mutsumi Ito1, Makoto Ozawa2,6, Tokiko Watanabe2, Saori Sakabe1,7, Chengjun Li2, Jin Hyun Kim2, Peter J. Myler4,8,9, Isabelle Phan4,8, Amy Raymond3,4, Eric Smith3,4, Robin Stacy4,8, Chairul A. Nidom10,11, Simon M. Lank12, Roger W. Wiseman12, Benjamin N. Bimber12, David H. O'Connor12,13, Gabriele Neumann2, Lance J. Stewart3,4*, Yoshihiro Kawaoka1,2,5,6,7,14*
1 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan, 2 Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 3 Emerald BioStructures, Inc., Bainbridge Island, Washington, United States of America, 4 Seattle Structural Genomics Center for Infectious Disease, Washington, United States of America, 5 Department of Microbiology and Infectious Diseases, Kobe University, Hyogo, Japan, 6 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan, 7 ERATO Infection-Induced Host Responses Project, Saitama, Japan, 8 Seattle Biomedical Research Institute, Seattle, Washington, United States of America, 9 Departments of Global Health and Medical Education & Biomedical Informatics, University of Washington, Seattle, Washington, United States of America, 10 Faculty of Veterinary Medicine, Tropical Disease Centre, Airlangga University, Surabaya, Indonesia, 11 Collaborating Research Center-Emerging and Reemerging Infectious Diseases, Tropical Disease Centre, Airlangga University, Surabaya, Indonesia, 12 Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 13 Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 14 Creative Research Initiative, Sousei, Hokkaido University, Sapporo, Japan
Abstract Top
Two amino acids (lysine at position 627 or asparagine at position 701) in the polymerase subunit PB2 protein are considered critical for the adaptation of avian influenza A viruses to mammals. However, the recently emerged pandemic H1N1 viruses lack these amino acids. Here, we report that a basic amino acid at position 591 of PB2 can compensate for the lack of lysine at position 627 and confers efficient viral replication to pandemic H1N1 viruses in mammals. Moreover, a basic amino acid at position 591 of PB2 substantially increased the lethality of an avian H5N1 virus in mice. We also present the X-ray crystallographic structure of the C-terminus of a pandemic H1N1 virus PB2 protein. Arginine at position 591 fills the cleft found in H5N1 PB2 proteins in this area, resulting in differences in surface shape and charge for H1N1 PB2 proteins. These differences may affect the protein's interaction with viral and/or cellular factors, and hence its ability to support virus replication in mammals.
full article
http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1001034