Residues in the PB2 and PA genes contribute to the pathogenicity of avian H7N3 influenza A virus in DBA/2 mice

Brittany L. DesRochers; Rita E. Chen; Anshu P. Gounder; Amelia K. Pinto; Traci Bricker; Camille N. Linton; Corianne D. Rogers; Graham D. Williams; Richard J. Webby; Adrianus C.M. Boon

doi:10.1016/j.virol.2016.04.013

Residues in the PB2 and PA genes contribute to the pathogenicity of avian H7N3 influenza A virus in DBA/2 mice

Brittany L. DesRochers, Rita E. Chen, Anshu P. Gounder, Amelia K. Pinto, Traci Bricker, Camille N. Linton, Corianne D. Rogers, Graham D. Williams, Richard J. Webby, Adrianus C.M. Boon

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Replication and transmission of avian influenza virus in humans poses a pandemic threat. The molecular determinants that facilitate this process are not well understood. We used DBA/2 mice to identify viral factors that mediate the difference in pathogenesis between a virulent (H7N3) and a non-virulent (H7N9) avian influenza virus from North America. In vitro and in vivo characterization of reassortant viruses identified the PB2 and PA polymerase genes as major determinants of H7N3 pathogenesis. Analysis of individual residues in the PB2 and PA genes identified position 358 (E₃₅₈V) in PB2 and positions 190 (P₁₉₀S) and 400 (Q₄₀₀P) in PA that reduced the virulence of H7N3 virus. The E₃₅₈V and P₁₉₀S substitutions also caused reduced inflammation after infection. Our results suggest that specific residues in the polymerase proteins PB2 and PA are important for replication and virulence of avian influenza viruses in a mammalian host.

Original language	English
Pages (from-to)	89-99
Number of pages	11
Journal	Virology
Volume	494
DOIs	https://doi.org/10.1016/j.virol.2016.04.013
State	Published - Jul 1 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

Avian influenza virus
DBA/2J
H7 subtype
Pathogenesis

ASJC Scopus subject areas

Virology

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title = "Residues in the PB2 and PA genes contribute to the pathogenicity of avian H7N3 influenza A virus in DBA/2 mice",

abstract = "Replication and transmission of avian influenza virus in humans poses a pandemic threat. The molecular determinants that facilitate this process are not well understood. We used DBA/2 mice to identify viral factors that mediate the difference in pathogenesis between a virulent (H7N3) and a non-virulent (H7N9) avian influenza virus from North America. In vitro and in vivo characterization of reassortant viruses identified the PB2 and PA polymerase genes as major determinants of H7N3 pathogenesis. Analysis of individual residues in the PB2 and PA genes identified position 358 (E358V) in PB2 and positions 190 (P190S) and 400 (Q400P) in PA that reduced the virulence of H7N3 virus. The E358V and P190S substitutions also caused reduced inflammation after infection. Our results suggest that specific residues in the polymerase proteins PB2 and PA are important for replication and virulence of avian influenza viruses in a mammalian host.",

keywords = "Avian influenza virus, DBA/2J, H7 subtype, Pathogenesis",

author = "DesRochers, {Brittany L.} and Chen, {Rita E.} and Gounder, {Anshu P.} and Pinto, {Amelia K.} and Traci Bricker and Linton, {Camille N.} and Rogers, {Corianne D.} and Williams, {Graham D.} and Webby, {Richard J.} and Boon, {Adrianus C.M.}",

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doi = "10.1016/j.virol.2016.04.013",

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AU - DesRochers, Brittany L.

AU - Chen, Rita E.

AU - Gounder, Anshu P.

AU - Pinto, Amelia K.

AU - Bricker, Traci

AU - Linton, Camille N.

AU - Rogers, Corianne D.

AU - Williams, Graham D.

AU - Webby, Richard J.

AU - Boon, Adrianus C.M.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Replication and transmission of avian influenza virus in humans poses a pandemic threat. The molecular determinants that facilitate this process are not well understood. We used DBA/2 mice to identify viral factors that mediate the difference in pathogenesis between a virulent (H7N3) and a non-virulent (H7N9) avian influenza virus from North America. In vitro and in vivo characterization of reassortant viruses identified the PB2 and PA polymerase genes as major determinants of H7N3 pathogenesis. Analysis of individual residues in the PB2 and PA genes identified position 358 (E358V) in PB2 and positions 190 (P190S) and 400 (Q400P) in PA that reduced the virulence of H7N3 virus. The E358V and P190S substitutions also caused reduced inflammation after infection. Our results suggest that specific residues in the polymerase proteins PB2 and PA are important for replication and virulence of avian influenza viruses in a mammalian host.

AB - Replication and transmission of avian influenza virus in humans poses a pandemic threat. The molecular determinants that facilitate this process are not well understood. We used DBA/2 mice to identify viral factors that mediate the difference in pathogenesis between a virulent (H7N3) and a non-virulent (H7N9) avian influenza virus from North America. In vitro and in vivo characterization of reassortant viruses identified the PB2 and PA polymerase genes as major determinants of H7N3 pathogenesis. Analysis of individual residues in the PB2 and PA genes identified position 358 (E358V) in PB2 and positions 190 (P190S) and 400 (Q400P) in PA that reduced the virulence of H7N3 virus. The E358V and P190S substitutions also caused reduced inflammation after infection. Our results suggest that specific residues in the polymerase proteins PB2 and PA are important for replication and virulence of avian influenza viruses in a mammalian host.

KW - Avian influenza virus

KW - DBA/2J

KW - H7 subtype

KW - Pathogenesis

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Residues in the PB2 and PA genes contribute to the pathogenicity of avian H7N3 influenza A virus in DBA/2 mice

Abstract

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Keywords

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