title: A 27-amino-acid deletion in the neuraminidase stalk supports replication of an avian H2N2 influenza A virus in the respiratory tract of chickens.
abstract: The events and mechanisms that lead to interspecies transmission of, and host adaptation to, influenza A virus are unknown; however, both surface and internal proteins have been implicated. Our previous report highlighted the role that Japanese quail play as an intermediate host, expanding the host range of a mallard H2N2 virus, A/mallard/Potsdam/178-4/83 (H2N2), through viral adaptation. This quail-adapted virus supported transmission in quail and increased its host range to replicate and be transmitted efficiently in chickens. Here we report that of the six amino acid changes in the quail-adapted virus, a single change in the hemagglutinin (HA) was crucial for transmission in quail, while the changes in the polymerase genes favored replication at lower temperatures than those for the wild-type mallard virus. Reverse genetic analysis indicated that all adaptive mutations were necessary for transmission in chickens, further implicating quail in extending this virus to terrestrial poultry. Adaptation of the quail-adapted virus in chickens resulted in the alteration of viral tropism from intestinal shedding to shedding and transmission via the respiratory tract. Sequence analysis indicated that this chicken-adapted virus maintained all quail-adaptive mutations, as well as an additional change in the HA and, most notably, a 27-amino-acid deletion in the stalk region of neuraminidase (NA), a genotypic marker of influenza virus adaptation to chickens. This stalk deletion was shown to be responsible for the change in virus tropism from the intestine to the respiratory tract.
authors.affiliation: Department of Virology, Erasmus Medical Center, Rotterdam, Netherlands. esorrell@umd.edu
authors.forename: Erin M
authors.initials: EM
authors.lastname: Sorrell
authors.forename: Haichen
authors.initials: H
authors.lastname: Song
authors.forename: Lindomar
authors.initials: L
authors.lastname: Pena
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Perez
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D003370:Coturnix; D053121:Influenza A Virus, H2N2 Subtype / Q000201:enzymology* / Q000235:genetics* / Q000502:physiology; D005585:Influenza in Birds / Q000821:virology*; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000235:genetics* / Q000378:metabolism; D011201:Poultry Diseases / Q000821:virology*; D011784:Quail; D012137:Respiratory System / Q000821:virology*; D017384:Sequence Deletion; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9654-8
references.pmid: 10920197
references.citation: J Virol. 2010 Jan;84(2):940-52
references.pmid: 19889765
references.citation: Annu Rev Microbiol. 2008;62:403-24
references.pmid: 18785841
references.citation: Avian Dis. 2007 Mar;51(1 Suppl):264-8
references.pmid: 17494563
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9363-7
references.pmid: 10430948
references.citation: PLoS One. 2008 Sep 09;3(9):e3170
references.pmid: 18779858
references.citation: Arch Virol. 2001 Dec;146(12):2275-89
references.pmid: 11811679
references.citation: PLoS Pathog. 2009 Mar;5(3):e1000350
references.pmid: 19300497
references.citation: J Virol. 1993 Feb;67(2):759-64
references.pmid: 8419645
references.citation: J Virol. 1999 Feb;73(2):1146-55
references.pmid: 9882316
references.citation: Virus Res. 2001 Nov 5;79(1-2):177-85
references.pmid: 11551658
references.citation: Vet Microbiol. 2011 Jan 10;147(1-2):59-66
references.pmid: 20619974
references.citation: J Infect Dis. 2007 Jul 15;196(2):258-65
references.pmid: 17570113
references.citation: Nature. 1982 Mar 11;296(5853):115-21
references.pmid: 6174870
references.citation: Arch Virol. 2001;146(5):963-73
references.pmid: 11448033
references.citation: Contrib Microbiol Immunol. 1987;8:20-59
references.pmid: 3304832
references.citation: Avian Pathol. 1986;15(4):647-62
references.pmid: 18766567
references.citation: J Virol. 2003 Mar;77(5):3148-56
references.pmid: 12584339
references.citation: J Infect Dis. 1997 Aug;176 Suppl 1:S14-9
references.pmid: 9240688
references.citation: Virology. 1999 Oct 25;263(2):323-38
references.pmid: 10544106
references.citation: N Engl J Med. 2009 Jun 18;360(25):2616-25
references.pmid: 19423871
references.citation: Virology. 2004 May 20;323(1):24-36
references.pmid: 15165816
references.citation: PLoS Pathog. 2009 Jan;5(1):e1000252
references.pmid: 19119420
references.citation: Science. 2009 Jun 19;324(5934):1557-61
references.pmid: 19433588
references.citation: Avian Dis. 2003;47(3 Suppl):1114-7
references.pmid: 14575124
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9345-50
references.pmid: 10430945
references.citation: Vaccine. 2002 Aug 19;20(25-26):3165-70
references.pmid: 12163268
references.citation: Virology. 1978 May 1;86(1):78-87
references.pmid: 664233
references.citation: Virus Genes. 2004 Aug;29(1):81-6
references.pmid: 15215686
references.citation: J Virol. 2007 Aug;81(16):8515-24
references.pmid: 17553873
references.citation: J Virol. 2007 May;81(10):5181-91
references.pmid: 17344280
references.citation: J Virol. 2001 Jun;75(11):5398-404
references.pmid: 11333924
references.citation: J Gen Virol. 2001 Oct;82(Pt 10):2475-2484
references.pmid: 11562540
references.citation: J Gen Virol. 2006 Jan;87(Pt 1):171-175
references.pmid: 16361429
references.citation: Virology. 1993 Jun;194(2):781-8
references.pmid: 7684877
references.citation: Virology. 2003 May 25;310(1):8-15
references.pmid: 12788625
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7712-8
references.pmid: 9223253
references.citation: Science. 2001 Sep 7;293(5536):1840-2
references.pmid: 11546875
references.citation: Virology. 2006 Mar 15;346(2):278-86
references.pmid: 16325879
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20949-54
references.pmid: 18093945
references.citation: J Gen Virol. 1999 Dec;80 ( Pt 12):3167-3171
references.pmid: 10567648
references.citation: J Gen Virol. 2000 May;81(Pt 5):1283-91
references.pmid: 10769071
references.citation: J Virol. 2002 Jan;76(2):507-16
references.pmid: 11752141
references.citation: Emerg Infect Dis. 2006 Sep;12(9):1353-60
references.pmid: 17073083
references.citation: Virology. 2000 Feb 15;267(2):279-88
references.pmid: 10662623