title: Intra- and interhost evolutionary dynamics of equine influenza virus.
abstract: Determining the evolutionary basis of cross-species transmission and immune evasion is key to understanding the mechanisms that control the emergence of either new viruses or novel antigenic variants with pandemic potential. The hemagglutinin glycoprotein of influenza A viruses is a critical host range determinant and a major target of neutralizing antibodies. Equine influenza virus (EIV) is a significant pathogen of the horse that causes periodical outbreaks of disease even in populations with high vaccination coverage. EIV has also jumped the species barrier and emerged as a novel respiratory pathogen in dogs, canine influenza virus. We studied the dynamics of equine influenza virus evolution in horses at the intrahost level and how this evolutionary process is affected by interhost transmission in a natural setting. To this end, we performed clonal sequencing of the hemagglutinin 1 gene derived from individual animals at different times postinfection. Our results show that despite the population consensus sequence remaining invariant, genetically distinct subpopulations persist during the course of infection and are also transmitted, with some variants likely to change antigenicity. We also detected a natural case of mixed infection in an animal infected during an outbreak of equine influenza, raising the possibility of reassortment between different strains of virus. In sum, our data suggest that transmission bottlenecks may not be as narrow as originally perceived and that the genetic diversity required to adapt to new host species may be partially present in the donor host and potentially transmitted to the recipient host.
authors.affiliation: Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, University of Cambridge, Madingley Road, CB3 0ES Cambridge, England, United Kingdom.
authors.forename: Pablo R
authors.initials: PR
authors.lastname: Murcia
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Baillie
authors.forename: Janet
authors.initials: J
authors.lastname: Daly
authors.forename: Debra
authors.initials: D
authors.lastname: Elton
authors.forename: Carley
authors.initials: C
authors.lastname: Jervis
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Mumford
authors.forename: Richard
authors.initials: R
authors.lastname: Newton
authors.forename: Colin R
authors.initials: CR
authors.lastname: Parrish
authors.forename: Karin
authors.initials: K
authors.lastname: Hoelzer
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Nicola
authors.initials: N
authors.lastname: Lennard
authors.forename: Doug
authors.initials: D
authors.lastname: Ormond
authors.forename: Sharon
authors.initials: S
authors.lastname: Moule
authors.forename: Andrew
authors.initials: A
authors.lastname: Whitwham
authors.forename: John W
authors.initials: JW
authors.lastname: McCauley
authors.forename: Trevelyan J
authors.initials: TJ
authors.lastname: McKinley
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Grenfell
authors.forename: James L N
authors.initials: JL
authors.lastname: Wood
mesh_terms: D000818:Animals; D004196:Disease Outbreaks / Q000662:veterinary; D004285:Dogs; D019143:Evolution, Molecular; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000145:classification / Q000235:genetics / Q000276:immunology; D006734:Horse Diseases / Q000453:epidemiology / Q000235:genetics / Q000635:transmission* / Q000821:virology*; D006736:Horses; D006801:Humans; D057131:Immune Evasion; D053123:Influenza A Virus, H3N8 Subtype / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D007251:Influenza, Human / Q000453:epidemiology / Q000235:genetics / Q000635:transmission / Q000821:virology; D016013:Likelihood Functions; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000453:epidemiology / Q000235:genetics / Q000635:transmission / Q000662:veterinary* / Q000821:virology; D010802:Phylogeny
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus
references.citation: Nature. 2005 Oct 6;437(7060):889-93
references.pmid: 16208372
references.citation: Vet Rec. 1988 Feb 6;122(6):125-8
references.pmid: 2835850
references.citation: Equine Vet J. 1990 Mar;22(2):93-8
references.pmid: 2156688
references.citation: Science. 2004 Jan 16;303(5656):327-32
references.pmid: 14726583
references.citation: Science. 2009 Jul 10;325(5937):197-201
references.pmid: 19465683
references.citation: Trends Ecol Evol. 2005 May;20(5):238-44
references.pmid: 16701375
references.citation: Proc Natl Acad Sci U S A. 2008 May 27;105(21):7552-7
references.pmid: 18490657
references.citation: N Engl J Med. 2005 Sep 29;353(13):1374-85
references.pmid: 16192482
references.citation: Genome Res. 1998 Mar;8(3):175-85
references.pmid: 9521921
references.citation: J Virol. 2000 Dec;74(24):11825-31
references.pmid: 11090182
references.citation: J Am Vet Med Assoc. 1963 Sep 15;143:587-90
references.pmid: 14077956
references.citation: Genome Res. 2001 Oct;11(10):1725-9
references.pmid: 11591649
references.citation: Bioinformatics. 2005 May 15;21(10):2531-3
references.pmid: 15713735
references.citation: Science. 2006 Nov 24;314(5803):1301-4
references.pmid: 17124322
references.citation: Virology. 1985 Dec;147(2):287-94
references.pmid: 2416114
references.citation: N Engl J Med. 2009 Jun 18;360(25):2605-15
references.pmid: 19423869
references.citation: PLoS Negl Trop Dis. 2009 Aug 04;3(8):e493
references.pmid: 19652703
references.citation: Science. 2008 Apr 18;320(5874):340-6
references.pmid: 18420927
references.citation: Emerg Infect Dis. 2008 Jun;14(6):902-8
references.pmid: 18507900
references.citation: Nature. 2008 May 29;453(7195):615-9
references.pmid: 18418375
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Sep 27;364(1530):2739-47
references.pmid: 19687042
references.citation: Nat Rev Genet. 2007 Mar;8(3):196-205
references.pmid: 17262054
references.citation: N Engl J Med. 2009 Jun 18;360(25):2616-25
references.pmid: 19423871
references.citation: J Biol Stand. 1983 Apr;11(2):133-6
references.pmid: 6408096
references.citation: Vet Rec. 2006 Feb 11;158(6):185-92
references.pmid: 16474051
references.citation: Vet Microbiol. 2009 Jul 2;138(1-2):41-52
references.pmid: 19346084
references.citation: Annu Rev Biochem. 1987;56:365-94
references.pmid: 3304138
references.citation: Nature. 2003 Dec 11;426(6967):658-61
references.pmid: 14668863
references.citation: Genome Res. 1998 Mar;8(3):186-94
references.pmid: 9521922
references.citation: Science. 2006 Apr 21;312(5772):394-7
references.pmid: 16627737
references.citation: J Virol Methods. 1988 May;20(1):1-12
references.pmid: 2840448
references.citation: J Virol. 1993 Apr;67(4):1761-4
references.pmid: 8445709
references.citation: Virology. 1978 Nov;91(1):79-85
references.pmid: 569394
references.citation: Bioinformatics. 1998;14(9):817-8
references.pmid: 9918953
references.citation: Science. 2005 Oct 21;310(5747):482-5
references.pmid: 16186182
references.citation: Arch Virol. 2001 Dec;146(12):2275-89
references.pmid: 11811679
references.citation: PLoS Biol. 2005 Sep;3(9):e300
references.pmid: 16026181
references.citation: Microbiol Rev. 1992 Mar;56(1):152-79
references.pmid: 1579108
references.citation: Virology. 1993 Jun;194(2):781-8
references.pmid: 7684877
references.citation: Annu Rev Microbiol. 1997;51:151-78
references.pmid: 9343347