Biological and Structural Characterization of a Host-Adapting Amino Acid in Influenza Virus

被引：267

作者：

Yamada, Shinya ^{[1
]}

Hatta, Masato ^{[2
]}

Staker, Bart L. ^{[3
,4
]}

Watanabe, Shinji ^{[2
]}

Imai, Masaki ^{[2
]}

Shinya, Kyoko ^{[5
]}

Sakai-Tagawa, Yuko ^{[1
]}

Ito, Mutsumi ^{[1
]}

Ozawa, Makoto ^{[2
,6
]}

Watanabe, Tokiko ^{[2
]}

Sakabe, Saori ^{[1
,7
]}

Li, Chengjun ^{[2
]}

Kim, Jin Hyun ^{[2
]}

Myler, Peter J. ^{[4
,8
,9
,10
]}

Phan, Isabelle ^{[4
,8
]}

Raymond, Amy ^{[3
,4
]}

Smith, Eric ^{[3
,4
]}

Stacy, Robin ^{[4
,8
]}

Nidom, Chairul A. ^{[11
,12
]}

Lank, Simon M. ^{[13
]}

Wiseman, Roger W. ^{[13
]}

Bimber, Benjamin N. ^{[13
]}

O'Connor, David H. ^{[13
,14
]}

Neumann, Gabriele ^{[2
]}

Stewart, Lance J. ^{[3
,4
]}

Kawaoka, Yoshihiro ^{[1
,2
,5
,6
,7
,15
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol, Tokyo, Japan

[2] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Influenza Res Inst, Madison, WI 53706 USA

[3] Emerald BioStruct Inc, Washington, DC USA

[4] Seattle Struct Genom Ctr Infect Dis, Washington, DC USA

[5] Kobe Univ, Dept Microbiol & Infect Dis, Kobe, Hyogo, Japan

[6] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Dept Special Pathogens, Tokyo, Japan

[7] ERATO Infect Induced Host Responses Project, Saitama, Japan

[8] Seattle Biomed Res Inst, Seattle, WA 98109 USA

[9] Univ Washington, Dept Global Hlth & Med Educ, Seattle, WA 98195 USA

[10] Univ Washington, Dept Biomed Informat, Seattle, WA 98195 USA

[11] Airlangga Univ, Trop Dis Ctr, Fac Vet Med, Surabaya, Indonesia

[12] Airlangga Univ, Trop Dis Ctr, Collaborating Res Ctr Emerging & Reemerging Infec, Surabaya, Indonesia

[13] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA

[14] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA

[15] Hokkaido Univ, Creat Res Initiat, Sapporo, Hokkaido, Japan

来源：

PLOS PATHOGENS | 2010年 / 6卷 / 08期

基金：

日本科学技术振兴机构;

关键词：

A VIRUS; PROTEIN CONSTRUCT; GENETIC-ANALYSIS; MOLECULAR-BASIS; PB2; TRANSMISSION; MOUSE; PATHOGENESIS; VIRULENCE; HA;

D O I：

10.1371/journal.ppat.1001034

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：15 / 16

页数：11

共 35 条

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