Differential use of importin-α isoforms governs cell tropism and host adaptation of influenza virus.
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-α, 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-α-silenced cells and importin-α-knockout mice, to understand the role of individual importin-α isoforms in adaptation. For efficient virus replication, the polymerase subunit PB2 and the nucleoprotein (NP) of avian viruses required importin-α3, whereas PB2 and NP of mammalian viruses showed importin-α7 specificity. H1N1v replication depended on both, importin-α3 and -α7, suggesting ongoing adaptation of this virus. Thus, differences in importin-α specificity are determinants of host range underlining the importance of the nuclear envelope in interspecies transmission.
1] Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany. [2] Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. [3] Institute of Virology, Philipps-University Marburg, Marburg, Germany.
Gülsah
G
Gabriel
Karin
K
Klingel
Anna
A
Otte
Swantje
S
Thiele
Ben
B
Hudjetz
Gökhan
G
Arman-Kalcek
Martina
M
Sauter
Tatiana
T
Shmidt
Franziska
F
Rother
Sigrid
S
Baumgarte
Björn
B
Keiner
Enno
E
Hartmann
Michael
M
Bader
George G
GG
Brownlee
Ervin
E
Fodor
Hans-Dieter
HD
Klenk
J Virol. 2005 Feb;79(4):2191-8
15681421
J Gen Virol. 2005 Feb;86(Pt 2):423-433
15659762
Am J Pathol. 2000 Jun;156(6):1951-9
10854218
Immunity. 2009 Feb 20;30(2):242-53
19200759
Am J Pathol. 2009 Sep;175(3):1178-86
19700749
Nucleic Acids Res. 2008 Dec;36(21):e139
18832366
Nature. 1980 Feb 14;283(5748):660-2
7354853
Science. 1998 Jan 16;279(5349):393-6
9430591
PLoS Pathog. 2008 Feb 8;4(2):e11
18248089
Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21312-6
19995968
Annu Rev Biochem. 1998;67:265-306
9759490
FEBS Lett. 1997 Nov 3;417(1):104-8
9395085
J Exp Med. 1976 May 1;143(5):1239-48
772154
Nature. 2009 Aug 20;460(7258):1021-5
19672242
J Virol. 2000 Sep;74(17):8018-27
10933711
Nat Cell Biol. 2007 Dec;9(12):1337-8; author reply 1339
18059353
Genome Biol. 2005;6(1):R6
15642098
J Virol. 1994 Nov;68(11):6900-9
7933070
J Immunol. 2008 Mar 1;180(5):3391-8
18292565
Nature. 2006 Mar 23;440(7083):435-6
16554799
Mol Cell Biol. 2006 Dec;26(23):8697-709
17000757
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4620-4
15070767
J Virol. 1997 Mar;71(3):1850-6
9032315
PLoS One. 2008;3(12):e3904
19066626
Science. 2009 Jul 24;325(5939):484-7
19574347
Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):314-8
1309611
Mol Cell Biol. 1999 Nov;19(11):7782-91
10523667
Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):582-7
9435235
Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7633-7
8052633
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18590-5
16339318
Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6156-60
8016130
J Exp Med. 1997 Dec 15;186(12):2063-8
9396777
Trends Immunol. 2009 Dec;30(12):574-84
19864182
J Virol. 1996 Dec;70(12):8888-95
8971018
Science. 2009 Jul 24;325(5939):481-3
19574348