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Structural Requirements in the Hemagglutinin Cleavage Site-Coding RNA Region for the Generation of Highly Pathogenic Avian Influenza Virus
| Title: | Structural Requirements in the Hemagglutinin Cleavage Site-Coding RNA Region for the Generation of Highly Pathogenic Avian Influenza Virus |
| Authors: | Kida, Yurie Browse this author | | Okuya, Kosuke Browse this author →KAKEN DB | | Saito, Takeshi Browse this author →KAKEN DB | | Yamagishi, Junya Browse this author →KAKEN DB | | Ohnuma, Aiko Browse this author | | Hattori, Takanari Browse this author | | Miyamoto, Hiroko Browse this author | | Manzoor, Rashid Browse this author | | Yoshida, Reiko Browse this author →KAKEN DB | | Nao, Naganori Browse this author →KAKEN DB | | Kajihara, Masahiro Browse this author →KAKEN DB | | Watanabe, Tokiko Browse this author →KAKEN DB | | Takada, Ayato Browse this author →KAKEN DB |
| Keywords: | influenza virus | | highly pathogenic avian influenza virus | | hemagglutinin | | cleavage site | | RNA secondary structure | | nucleotide insertion |
| Issue Date: | Dec-2021 |
| Publisher: | MDPI |
| Journal Title: | Pathogens |
| Volume: | 10 |
| Issue: | 12 |
| Start Page: | 1597 |
| Publisher DOI: | 10.3390/pathogens10121597 |
| 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/84077 |
| Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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