TY - JOUR

T1 - Replication, pathogenesis and transmission of pandemic (H1N1) 2009 virus in non-immune pigs

AU - Brookes, Sharon M.

AU - Núñez, Alejandro

AU - Choudhury, Bhudipa

AU - Matrosovich, Mikhail

AU - Essen, Stephen C.

AU - Clifford, Derek

AU - Slomka, Marek J.

AU - Kuntz-Simon, Gaëlle

AU - Garcon, Fanny

AU - Nash, Bethany

AU - Hanna, Amanda

AU - Heegaard, Peter M.H.

AU - Quéguiner, Stéphane

AU - Chiapponi, Chiara

AU - Bublot, Michel

AU - Garcia, Jaime Maldonado

AU - Gardner, Rebecca

AU - Foni, Emanuela

AU - Loeffen, Willie

AU - Larsen, Lars

AU - Van Reeth, Kristien

AU - Banks, Jill

AU - Irvine, Richard M.

AU - Brown, Ian H.

PY - 2010/2/5

Y1 - 2010/2/5

N2 - 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].

AB - 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].

UR - http://www.scopus.com/inward/record.url?scp=77949371043&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0009068

DO - 10.1371/journal.pone.0009068

M3 - Journal article

C2 - 20140096

AN - SCOPUS:77949371043

VL - 5

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 2

M1 - e9068

ER -