H7N9 influenza virus containing a polybasic HA cleavage site requires minimal host adaptation to obtain a highly pathogenic disease phenotype in mice

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creativework.keywords - en
Avian influenza
creativework.keywords - fr
Grippe aviaire
dc.contributor.author
Chan, Mable
Leung, Anders
Hisanaga, Tamiko
Pickering, Brad
Griffin, Bryan D.
Vendramelli, Robert
Tailor, Nikesh
Wong, Gary
Bi, Yuhai
Babiuk, Shawn
Berhane, Yohannes
Kobasa, Darwyn
dc.date.accepted
2020-01-03
dc.date.accessioned
2025-04-09T20:43:12Z
dc.date.available
2025-04-09T20:43:12Z
dc.date.issued
2020-01-05
dc.date.submitted
2019-09-14
dc.description.abstract - en
Low pathogenic avian influenza (LPAI) H7N9 viruses have recently evolved to gain a polybasic cleavage site in the hemagglutinin (HA) protein, resulting in variants with increased lethality in poultry that meet the criteria for highly pathogenic avian influenza (HPAI) viruses. Both LPAI and HPAI variants can cause severe disease in humans (case fatality rate of ~40%). Here, we investigated the virulence of HPAI H7N9 viruses containing a polybasic HA cleavage site (H7N9-PBC) in mice. Inoculation of mice with H7N9-PBC did not result in observable disease; however, mice inoculated with a mouse-adapted version of this virus, generated by a single passage in mice, caused uniformly lethal disease. In addition to the PBC site, we identified three other mutations that are important for host-adaptation and virulence in mice: HA (A452T), PA (D347G), and PB2 (M483K). Using reverse genetics, we confirmed that the HA mutation was the most critical for increased virulence in mice. Our study identifies additional disease determinants in a mammalian model for HPAI H7N9 virus. Furthermore, the ease displayed by the virus to adapt to a new host highlights the potential for H7N9-PBC viruses to rapidly acquire mutations that may enhance their risk to humans or other animal species.
dc.identifier.citation
Chan, M., Leung, A., Hisanaga, T., Pickering, B., Griffin, B. D., Vendramelli, R., Tailor, N., Wong, G., Bi, Y., Babiuk, S., Berhane, Y., & Kobasa, D. (2020). H7N9 influenza virus containing a polybasic HA cleavage site requires minimal host adaptation to obtain a highly pathogenic disease phenotype in mice. Viruses, 12(1), 65. https://doi.org/10.3390/v12010065
dc.identifier.doi
https://doi.org/10.3390/v12010065
dc.identifier.issn
1999-4915
dc.identifier.uri
https://open-science.canada.ca/handle/123456789/3598
dc.language.iso
en
dc.publisher - en
MDPI
dc.rights - en
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights - fr
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights.openaccesslevel - en
Gold
dc.rights.openaccesslevel - fr
Or
dc.rights.uri - en
https://creativecommons.org/licenses/by/4.0/
dc.rights.uri - fr
https://creativecommons.org/licenses/by/4.0/deed.fr
dc.subject - en
Viruses
Rodents
Influenza
dc.subject - fr
Virus
Rongeur
Grippe
dc.subject.en - en
Viruses
Rodents
Influenza
dc.subject.fr - fr
Virus
Rongeur
Grippe
dc.title - en
H7N9 influenza virus containing a polybasic HA cleavage site requires minimal host adaptation to obtain a highly pathogenic disease phenotype in mice
dc.type - en
Article
dc.type - fr
Article
local.article.journalissue
1
local.article.journaltitle - en
Viruses
local.article.journalvolume
12
local.pagination
65
local.peerreview - en
Yes
local.peerreview - fr
Oui
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