Contribution of the NS1 Gene of H7 Avian Influenza Virus Strains to Pathogenicity in Chickens

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Using reverse genetics (rg), we generated two reassortant viruses carrying the NS1 gene of two closely related HPAIV and LPAIV H7N1 variants (designated rgH7N7 HPHPNS1 and rgH7N7 HPLPNS1, respectively) in the backbone of the HP H7N7 strain A/Chicken/Netherlands/621557/03 (rgH7N7 HP). Comparison of these reassortants allowed us to determine the effect of amino acid differences in the nuclear export and nucleolar localization sequences of NS1 on pathogenesis in chickens. Compared to rgH7N7 HPLPNS1, a delay in weight gain and an increase in mortality were observed for rgH7N7 HPHPNS1. Furthermore, an increase in viral load in brains, lungs, and cloacal swabs, as well as an increased induction of mRNA for type I interferons and proinflammatory cytokines in brains, were observed for rgH7N7 HPHPNS1. Comparison of rgH7N7 HPLPNS1 with the backbone strain rgH7N7 HP allowed us to examine differences in pathogenesis due to differences in NS1 alleles. rgH7N7 HP, which contained allele A of NS1 showed a higher in vitro replication rate and proved to be more virulent than the isogenic virus carrying allele B of NS1(rgH7N7 HPLPNS1). In addition, higher virus accumulation in the lungs and brains, and an increased induction of host gene responses, especially in the brains, were found for rgH7N7 HP compared to rgH7N7 HPLPNS1. No large differences were observed in type I interferon expression in the lungs of chickens infected with any of the viruses, suggesting that differences in virulence due to differences in NS1 could be related to differences in the induction of pro-inflammatory cytokines in vital organs such as the brains.
Original languageEnglish
Pages (from-to)396-403
JournalViral Immunology
Volume26
Issue number6
DOIs
Publication statusPublished - 2013

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Influenza in Birds
Orthomyxoviridae
Virulence
Chickens
Brain
Interferon Type I
Genes
Alleles
Viruses
Lung
Reassortant Viruses
Cytokines
Reverse Genetics
Cell Nucleus Active Transport
Viral Load
Netherlands
Weight Gain
Amino Acids
Messenger RNA
Mortality

Keywords

  • a virus
  • nonstructural protein-1
  • cytokine responses
  • interferon
  • h5n1
  • infection
  • virulence
  • cells
  • ducks
  • beta

Cite this

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title = "Contribution of the NS1 Gene of H7 Avian Influenza Virus Strains to Pathogenicity in Chickens",
abstract = "Using reverse genetics (rg), we generated two reassortant viruses carrying the NS1 gene of two closely related HPAIV and LPAIV H7N1 variants (designated rgH7N7 HPHPNS1 and rgH7N7 HPLPNS1, respectively) in the backbone of the HP H7N7 strain A/Chicken/Netherlands/621557/03 (rgH7N7 HP). Comparison of these reassortants allowed us to determine the effect of amino acid differences in the nuclear export and nucleolar localization sequences of NS1 on pathogenesis in chickens. Compared to rgH7N7 HPLPNS1, a delay in weight gain and an increase in mortality were observed for rgH7N7 HPHPNS1. Furthermore, an increase in viral load in brains, lungs, and cloacal swabs, as well as an increased induction of mRNA for type I interferons and proinflammatory cytokines in brains, were observed for rgH7N7 HPHPNS1. Comparison of rgH7N7 HPLPNS1 with the backbone strain rgH7N7 HP allowed us to examine differences in pathogenesis due to differences in NS1 alleles. rgH7N7 HP, which contained allele A of NS1 showed a higher in vitro replication rate and proved to be more virulent than the isogenic virus carrying allele B of NS1(rgH7N7 HPLPNS1). In addition, higher virus accumulation in the lungs and brains, and an increased induction of host gene responses, especially in the brains, were found for rgH7N7 HP compared to rgH7N7 HPLPNS1. No large differences were observed in type I interferon expression in the lungs of chickens infected with any of the viruses, suggesting that differences in virulence due to differences in NS1 could be related to differences in the induction of pro-inflammatory cytokines in vital organs such as the brains.",
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author = "J. Post and B.P.H. Peeters and J.B.W.J. Cornelissen and L. Vervelde and J.M.J. Rebel",
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Contribution of the NS1 Gene of H7 Avian Influenza Virus Strains to Pathogenicity in Chickens. / Post, J.; Peeters, B.P.H.; Cornelissen, J.B.W.J.; Vervelde, L.; Rebel, J.M.J.

In: Viral Immunology, Vol. 26, No. 6, 2013, p. 396-403.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Post, J.

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KW - a virus

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KW - h5n1

KW - infection

KW - virulence

KW - cells

KW - ducks

KW - beta

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