Altered virulence of Highly Pathogenic Avian Influenza (HPAI) H5N8 reassortant viruses in mammalian models

Su Jin Park, Eun Ha Kim, Hyeok Il Kwon, Min Suk Song, Se Mi Kim, Young Il Kim, Young Jae Si, In Won Lee, Hiep Dinh Nguyen, Ok Shin, Chul Joong Kim, Young Ki Choi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Recently identified highly pathogenic avian influenza (HPAI) H5N8 viruses (clade 2.3.4.4) are relatively low to moderately pathogenic in mammalian hosts compared with HPAI H5N1 viruses. In this study, we generated reassortant viruses comprised of A/MD/Korea/W452/2014(H5N8) with substitution of individual genes from A/EM/Korea/W149/2006(H5N1) to understand the contribution of each viral gene to virulence in mammals. Substituting the PB2 gene segment or the NA gene segment of the H5N8 virus by that from the H5N1 virus resulted in significantly enhanced pathogenicity compared with the parental H5N8 virus in mice. Of note, substitution of the PB2 gene segment of the H5N8 virus by that from the H5N1 virus resulted in a 1000-fold increase in virulence for mice compared with the parental virus (MLD50 decreased from 105.8 to 102.5 EID50). Further, the W452W149PB2 virus also induced the highest virus titers in lungs at all time points and the highest levels of inflammatory cytokine responses among all viruses tested. This high virulence phenotype was also confirmed by high viral titers in the respiratory tracts of infected ferrets. Further, a mini-genome assay revealed that W452W149PB2 has significantly increased polymerase activity (p < 0.001). Taken together, our study demonstrates that a single gene substitution from other avian influenza viruses can alter the pathogenicity of recent H5N8 viruses, and therefore emphasizes the need for intensive monitoring of reassortment events among co-circulating avian and mammalian viruses.

Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournalVirulence
DOIs
Publication statusAccepted/In press - 2017 Sep 19

Fingerprint

Reassortant Viruses
Influenza in Birds
Orthomyxoviridae
Virulence
H5N1 Subtype Influenza A Virus
Viruses
Genes
Korea
Ferrets
Viral Genes
Viral Load
Respiratory System
Mammals
H5N8 Subtype Influenza A Virus
Genome
Cytokines
Phenotype
Lung

Keywords

  • H5N8
  • HPAI influenza virus
  • PB2
  • reassortment
  • virulence

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Park, S. J., Kim, E. H., Kwon, H. I., Song, M. S., Kim, S. M., Kim, Y. I., ... Choi, Y. K. (Accepted/In press). Altered virulence of Highly Pathogenic Avian Influenza (HPAI) H5N8 reassortant viruses in mammalian models. Virulence, 1-17. https://doi.org/10.1080/21505594.2017.1366408

Altered virulence of Highly Pathogenic Avian Influenza (HPAI) H5N8 reassortant viruses in mammalian models. / Park, Su Jin; Kim, Eun Ha; Kwon, Hyeok Il; Song, Min Suk; Kim, Se Mi; Kim, Young Il; Si, Young Jae; Lee, In Won; Nguyen, Hiep Dinh; Shin, Ok; Kim, Chul Joong; Choi, Young Ki.

In: Virulence, 19.09.2017, p. 1-17.

Research output: Contribution to journalArticle

Park, SJ, Kim, EH, Kwon, HI, Song, MS, Kim, SM, Kim, YI, Si, YJ, Lee, IW, Nguyen, HD, Shin, O, Kim, CJ & Choi, YK 2017, 'Altered virulence of Highly Pathogenic Avian Influenza (HPAI) H5N8 reassortant viruses in mammalian models', Virulence, pp. 1-17. https://doi.org/10.1080/21505594.2017.1366408
Park, Su Jin ; Kim, Eun Ha ; Kwon, Hyeok Il ; Song, Min Suk ; Kim, Se Mi ; Kim, Young Il ; Si, Young Jae ; Lee, In Won ; Nguyen, Hiep Dinh ; Shin, Ok ; Kim, Chul Joong ; Choi, Young Ki. / Altered virulence of Highly Pathogenic Avian Influenza (HPAI) H5N8 reassortant viruses in mammalian models. In: Virulence. 2017 ; pp. 1-17.
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abstract = "Recently identified highly pathogenic avian influenza (HPAI) H5N8 viruses (clade 2.3.4.4) are relatively low to moderately pathogenic in mammalian hosts compared with HPAI H5N1 viruses. In this study, we generated reassortant viruses comprised of A/MD/Korea/W452/2014(H5N8) with substitution of individual genes from A/EM/Korea/W149/2006(H5N1) to understand the contribution of each viral gene to virulence in mammals. Substituting the PB2 gene segment or the NA gene segment of the H5N8 virus by that from the H5N1 virus resulted in significantly enhanced pathogenicity compared with the parental H5N8 virus in mice. Of note, substitution of the PB2 gene segment of the H5N8 virus by that from the H5N1 virus resulted in a 1000-fold increase in virulence for mice compared with the parental virus (MLD50 decreased from 105.8 to 102.5 EID50). Further, the W452W149PB2 virus also induced the highest virus titers in lungs at all time points and the highest levels of inflammatory cytokine responses among all viruses tested. This high virulence phenotype was also confirmed by high viral titers in the respiratory tracts of infected ferrets. Further, a mini-genome assay revealed that W452W149PB2 has significantly increased polymerase activity (p < 0.001). Taken together, our study demonstrates that a single gene substitution from other avian influenza viruses can alter the pathogenicity of recent H5N8 viruses, and therefore emphasizes the need for intensive monitoring of reassortment events among co-circulating avian and mammalian viruses.",
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