Differential use of importin-α isoforms governs cell tropism and host adaptation of influenza virus

被引：198

作者：

Gabriel, Guelsah ^{[1
,2
,3
]}

Klingel, Karin ^{[4
]}

Otte, Anna ^{[1
]}

Thiele, Swantje ^{[1
]}

Hudjetz, Ben ^{[1
]}

Arman-Kalcek, Goekhan ^{[1
]}

Sauter, Martina ^{[4
]}

Shmidt, Tatiana ^{[5
]}

Rother, Franziska ^{[5
]}

Baumgarte, Sigrid ^{[6
]}

Keiner, Bjoern ^{[3
]}

Hartmann, Enno ^{[7
]}

Bader, Michael ^{[5
]}

Brownlee, George G. ^{[2
]}

Fodor, Ervin ^{[2
]}

Klenk, Hans-Dieter ^{[3
]}

机构：

[1] Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany

[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[3] Univ Marburg, Inst Virol, D-3550 Marburg, Germany

[4] Univ Tubingen Hosp, Inst Pathol, Tubingen, Germany

[5] Max Delbruck Ctr Mol Med, Berlin, Germany

[6] Inst Hyg & Environm, Hamburg, Germany

[7] Med Univ Lubeck, Inst Biol, D-23538 Lubeck, Germany

来源：

NATURE COMMUNICATIONS | 2011年 / 2卷

关键词：

NUCLEAR-LOCALIZATION SIGNAL; A VIRUS; DEFICIENT-MICE; HUMAN AIRWAY; IN-VITRO; PROTEIN; INFECTION; PATHOGENESIS; POLYMERASE; FERRETS;

D O I：

10.1038/ncomms1158

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Influenza A viruses are a threat to humans due to their ability to cross species barriers, as illustrated by the 2009 H1N1v pandemic and sporadic H5N1 transmissions. Interspecies transmission requires adaptation of the viral polymerase to importin-alpha, a cellular protein that mediates transport into the nucleus where transcription and replication of the viral genome takes place. In this study, we analysed replication, host specificity and pathogenicity of avian and mammalian influenza viruses, in importin-alpha-silenced cells and importin-alpha-knockout mice, to understand the role of individual importin-alpha isoforms in adaptation. For efficient virus replication, the polymerase subunit PB2 and the nucleoprotein (NP) of avian viruses required importin-alpha 3, whereas PB2 and NP of mammalian viruses showed importin-alpha 7 specificity. H1N1v replication depended on both, importin-alpha 3 and -alpha 7, suggesting ongoing adaptation of this virus. Thus, differences in importin-alpha specificity are determinants of host range underlining the importance of the nuclear envelope in interspecies transmission.

引用

页数：7

共 35 条

[1]

BARCENA J, 1994, J VIROL, V68, P6900

[2] Full-length cDNAs from chicken bursal lymphocytes to facilitate gene function analysis [J].

Randolph B Caldwell ;

Andrzej M Kierzek ;

Hiroshi Arakawa ;

Yuri Bezzubov ;

Jolanta Zaim ;

Petra Fiedler ;

Stefan Kutter ;

Artem Blagodatski ;

Diyana Kostovska ;

Marek Koter ;

Jiri Plachy ;

Piero Carninci ;

Yoshihide Hayashizaki ;

Jean-Marie Buerstedde .

Genome Biology, 6 (1)

[3] RAG-1 INTERACTS WITH THE REPEATED AMINO-ACID MOTIF OF THE HUMAN HOMOLOG OF THE YEAST PROTEIN SRP1 [J].

CORTES, P ;

YE, ZS ;

BALTIMORE, D .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7633-7637

[4] RCH1, A PROTEIN THAT SPECIFICALLY INTERACTS WITH THE RAG-1 RECOMBINATION-ACTIVATING PROTEIN [J].

CUOMO, CA ;

KIRCH, SA ;

GYURIS, J ;

BRENT, R ;

OETTINGER, MA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (13) :6156-6160

[5] Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus [J].

Dawson, TC ;

Beck, MA ;

Kuziel, WA ;

Henderson, F ;

Maeda, N .

AMERICAN JOURNAL OF PATHOLOGY, 2000, 156 (06) :1951-1959

[6] Targeted infection of endothelial cells by avian influenza virus A/FPV/Rostock/34 (H7N1) in chicken embryos [J].

Feldmann, A ;

Schäfer, MKH ;

Garten, W ;

Klenk, HD .

JOURNAL OF VIROLOGY, 2000, 74 (17) :8018-8027

[7] Nuclear localization signal and protein context both mediate importin at specificity of nuclear import substrates [J].

Friedrich, Beate ;

Quensel, Christina ;

Sommer, Thomas ;

Hartmann, Enno ;

Koehler, Matthias .

MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (23) :8697-8709

[8] The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host [J].

Gabriel, G ;

Dauber, B ;

Wolff, T ;

Planz, O ;

Klenk, HD ;

Stech, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (51) :18590-18595

[9] Interaction of polymerase subunit PB2 and NP with importin α1 is a determinant of host range of influenza a virus [J].

Gabriel, Guelsah ;

Herwig, Astrid ;

Klenk, Hans-Dieter .

PLOS PATHOGENS, 2008, 4 (02)

[10] Spread of Infection and Lymphocyte Depletion in Mice Depends on Polymerase of Influenza Virus [J].

Gabriel, Guelsah ;

Klingel, Karin ;

Planz, Oliver ;

Bier, Katja ;

Herwig, Astrid ;

Sauter, Martina ;

Klenk, Hans-Dieter .

AMERICAN JOURNAL OF PATHOLOGY, 2009, 175 (03) :1178-1186

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