Intra- and interhost evolutionary dynamics of equine influenza virus.
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.
Murcia
Pablo R
PR
Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, University of Cambridge, Madingley Road, CB3 0ES Cambridge, England, United Kingdom.
Baillie
Gregory J
GJ
Daly
Janet
J
Elton
Debra
D
Jervis
Carley
C
Mumford
Jennifer A
JA
Newton
Richard
R
Parrish
Colin R
CR
Hoelzer
Karin
K
Dougan
Gordon
G
Parkhill
Julian
J
Lennard
Nicola
N
Ormond
Doug
D
Moule
Sharon
S
Whitwham
Andrew
A
McCauley
John W
JW
McKinley
Trevelyan J
TJ
Holmes
Edward C
EC
Grenfell
Bryan T
BT
Wood
James L N
JL
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
D019267:Hemagglutinin Glycoproteins, Influenza Virus
Nature. 2005 Oct 6;437(7060):889-93
16208372
Vet Rec. 1988 Feb 6;122(6):125-8
2835850
Equine Vet J. 1990 Mar;22(2):93-8
2156688
Science. 2004 Jan 16;303(5656):327-32
14726583
Science. 2009 Jul 10;325(5937):197-201
19465683
Trends Ecol Evol. 2005 May;20(5):238-44
16701375
Proc Natl Acad Sci U S A. 2008 May 27;105(21):7552-7
18490657
N Engl J Med. 2005 Sep 29;353(13):1374-85
16192482
Genome Res. 1998 Mar;8(3):175-85
9521921
J Virol. 2000 Dec;74(24):11825-31
11090182
J Am Vet Med Assoc. 1963 Sep 15;143:587-90
14077956
Genome Res. 2001 Oct;11(10):1725-9
11591649
Bioinformatics. 2005 May 15;21(10):2531-3
15713735
Science. 2006 Nov 24;314(5803):1301-4
17124322
Virology. 1985 Dec;147(2):287-94
2416114
N Engl J Med. 2009 Jun 18;360(25):2605-15
19423869
PLoS Negl Trop Dis. 2009 Aug 04;3(8):e493
19652703
Science. 2008 Apr 18;320(5874):340-6
18420927
Emerg Infect Dis. 2008 Jun;14(6):902-8
18507900
Nature. 2008 May 29;453(7195):615-9
18418375
Philos Trans R Soc Lond B Biol Sci. 2009 Sep 27;364(1530):2739-47
19687042
Nat Rev Genet. 2007 Mar;8(3):196-205
17262054
N Engl J Med. 2009 Jun 18;360(25):2616-25
19423871
J Biol Stand. 1983 Apr;11(2):133-6
6408096
Vet Rec. 2006 Feb 11;158(6):185-92
16474051
Vet Microbiol. 2009 Jul 2;138(1-2):41-52
19346084
Annu Rev Biochem. 1987;56:365-94
3304138
Nature. 2003 Dec 11;426(6967):658-61
14668863
Genome Res. 1998 Mar;8(3):186-94
9521922
Science. 2006 Apr 21;312(5772):394-7
16627737
J Virol Methods. 1988 May;20(1):1-12
2840448
J Virol. 1993 Apr;67(4):1761-4
8445709
Virology. 1978 Nov;91(1):79-85
569394
Bioinformatics. 1998;14(9):817-8
9918953
Science. 2005 Oct 21;310(5747):482-5
16186182
Arch Virol. 2001 Dec;146(12):2275-89
11811679
PLoS Biol. 2005 Sep;3(9):e300
16026181
Microbiol Rev. 1992 Mar;56(1):152-79
1579108
Virology. 1993 Jun;194(2):781-8
7684877
Annu Rev Microbiol. 1997;51:151-78
9343347