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Production of High-Titer Infectious Influenza Pseudotyped Particles with Envelope Glycoproteins from Highly Pathogenic H5N1 and Avian H7N9 Viruses
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Production of High-Titer Infectious Influenza Pseudotyped Particles with Envelope Glycoproteins from Highly Pathogenic H5N1 and Avian H7N9 Viruses

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The molecular basis of the pathogenicity of the Dutch highly pathogenic human influenza A H7N7 viruses

Vincent J Munster1, Emmie de Wit, Debby van Riel

  • 1Department of Virology and National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands.

The Journal of Infectious Diseases
|June 16, 2007
PubMed

Insights

The lysine at position 627 in the PB2 gene of the highly pathogenic avian influenza (HPAI) H7N7 virus was the main factor determining its severity and spread in the body. This finding is crucial for monitoring zoonotic HPAI outbreaks.

Area of Science:

  • Virology
  • Molecular Biology
  • Epidemiology

Background:

  • The 2003 highly pathogenic avian influenza (HPAI) H7N7 outbreak in The Netherlands resulted in mild illness for most, but one fatality due to pneumonia.
  • Understanding the genetic determinants of HPAI pathogenicity is critical for public health surveillance.

Purpose of the Study:

  • To identify specific amino acid substitutions responsible for the differing pathogenicity between a fatal case (FC) H7N7 virus and a conjunctivitis case (CC) H7N7 virus.
  • To investigate the role of viral genes in tissue tropism and pathogenicity.

Main Methods:

  • Comparative analysis of viral genetic sequences from fatal and mild H7N7 cases.
  • In vitro virus-attachment assays to assess binding to human respiratory tract tissues.
  • In vivo pathogenicity and tissue distribution studies using a mouse model.

Main Results:

  • Significant differences in binding affinity to the lower respiratory tract were observed between CC and FC viruses.
  • The hemagglutinin (HA) gene of the FC virus influenced viral tissue distribution in mice.
  • A specific mutation, lysine at position 627 of the PB2 gene in the FC virus, was identified as the primary determinant of pathogenicity and tissue distribution.
  • Similarities were noted between H7N7 and H5N1 HPAI viruses regarding key genetic determinants.

Conclusions:

  • The PB2 gene, specifically lysine at position 627, plays a critical role in HPAI H7N7 pathogenicity and tissue tropism.
  • The HA and PB2 genes are key targets for molecular surveillance of zoonotic HPAI viruses during outbreaks.
  • Findings highlight the importance of continuous monitoring of avian influenza viruses for potential human health risks.

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