Replication, pathogenesis and transmission of pandemic (H1N1) 2009 virus in non-immune pigs.
The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range [1], [2]. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment and evolution within swine worldwide [3]. A key public and veterinary health consideration in the context of the evolving pandemic is whether the H1N1/09 virus could become established in pig populations [4]. We performed an infection and transmission study in pigs with A/California/07/09. In combination, clinical, pathological, modified influenza A matrix gene real time RT-PCR and viral genomic analyses have shown that infection results in the induction of clinical signs, viral pathogenesis restricted to the respiratory tract, infection dynamics consistent with endemic strains of influenza A in pigs, virus transmissibility between pigs and virus-host adaptation events. Our results demonstrate that extant H1N1/09 is fully capable of becoming established in global pig populations. We also show the roles of viral receptor specificity in both transmission and tissue tropism. Remarkably, following direct inoculation of pigs with virus quasispecies differing by amino acid substitutions in the haemagglutinin receptor-binding site, only virus with aspartic acid at position 225 (225D) was detected in nasal secretions of contact infected pigs. In contrast, in lower respiratory tract samples from directly inoculated pigs, with clearly demonstrable pulmonary pathology, there was apparent selection of a virus variant with glycine (225G). These findings provide potential clues to the existence and biological significance of viral receptor-binding variants with 225D and 225G during the 1918 pandemic [5].
Veterinary Laboratories Agency-Weybridge, EU/OIE/FAO Reference Laboratory for Avian Influenza and Newcastle Disease, Addlestone, Surrey, United Kingdom.
Sharon M
SM
Brookes
Alejandro
A
Núñez
Bhudipa
B
Choudhury
Mikhail
M
Matrosovich
Stephen C
SC
Essen
Derek
D
Clifford
Marek J
MJ
Slomka
Gaëlle
G
Kuntz-Simon
Fanny
F
Garcon
Bethany
B
Nash
Amanda
A
Hanna
Peter M H
PM
Heegaard
Stéphane
S
Quéguiner
Chiara
C
Chiapponi
Michel
M
Bublot
Jaime Maldonado
JM
Garcia
Rebecca
R
Gardner
Emanuela
E
Foni
Willie
W
Loeffen
Lars
L
Larsen
Kristien
K
Van Reeth
Jill
J
Banks
Richard M
RM
Irvine
Ian H
IH
Brown
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology; D001483:Base Sequence; D002642:Chick Embryo; D004196:Disease Outbreaks; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000635:transmission / Q000662:veterinary*; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013552:Swine; D013553:Swine Diseases / Q000473:pathology / Q000821:virology*; D014763:Viral Matrix Proteins / Q000235:genetics; D014779:Virus Replication
D000956:Antigens, Viral; D006389:Hemagglutinins, Viral; D014763:Viral Matrix Proteins