Structural requirements in the hemagglutinin cleavage site-coding rna region for the generation of highly pathogenic avian influenza virus

Yurie Kida, Kosuke Okuya, Takeshi Saito, Junya Yamagishi, Aiko Ohnuma, Takanari Hattori, Hiroko Miyamoto, Rashid Manzoor, Reiko Yoshida, Naganori Nao, Masahiro Kajihara, Tokiko Watanabe, Ayato Takada

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Highly pathogenic avian influenza viruses (HPAIVs) with H5 and H7 hemagglutinin (HA) subtypes are derived from their low pathogenic counterparts following the acquisition of multiple basic amino acids in their HA cleavage site. It has been suggested that consecutive adenine residues and a stem-loop structure in the viral RNA region that encodes the cleavage site are essential for the acquisition of the polybasic cleavage site. By using a reporter assay to detect non-templated nucleotide insertions, we found that insertions more frequently occurred in the RNA region (29 nucleotide-length) encoding the cleavage site of an H5 HA gene that was predicted to have a stem-loop structure containing consecutive adenines than in a mutated corresponding RNA region that had a disrupted loop structure with fewer adenines. In virus particles generated by using reverse genetics, nucleotide insertions that created additional codons for basic amino acids were found in the RNA region encoding the cleavage site of an H5 HA gene but not in the mutated RNA region. We confirmed the presence of virus clones with the ability to replicate without trypsin in a plaque assay and to cause lethal infection in chicks. These results demonstrate that the stem-loop structure containing consecutive adenines in HA genes is a key molecular determinant for the emergence of H5 HPAIVs.

Original languageEnglish (US)
Article number1597
JournalPathogens
Volume10
Issue number12
DOIs
StatePublished - Dec 2021
Externally publishedYes

Keywords

  • Cleavage site
  • Hemagglutinin
  • Highly pathogenic avian influenza virus
  • Influenza virus
  • Nucleotide insertion
  • RNA secondary structure

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • General Immunology and Microbiology
  • Microbiology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Structural requirements in the hemagglutinin cleavage site-coding rna region for the generation of highly pathogenic avian influenza virus'. Together they form a unique fingerprint.

Cite this