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HA stabilization promotes replication and transmission of swine H1N1 gamma influenza viruses in ferrets.


ABSTRACT: Pandemic influenza A viruses can emerge from swine, an intermediate host that supports adaptation of human-preferred receptor-binding specificity by the hemagglutinin (HA) surface antigen. Other HA traits necessary for pandemic potential are poorly understood. For swine influenza viruses isolated in 2009-2016, gamma-clade viruses had less stable HA proteins (activation pH 5.5-5.9) than pandemic clade (pH 5.0-5.5). Gamma-clade viruses replicated to higher levels in mammalian cells than pandemic clade. In ferrets, a model for human adaptation, a relatively stable HA protein (pH 5.5-5.6) was necessary for efficient replication and airborne transmission. The overall airborne transmission frequency in ferrets for four isolates tested was 42%, and isolate G15 airborne transmitted 100% after selection of a variant with a stabilized HA. The results suggest swine influenza viruses containing both a stabilized HA and alpha-2,6 receptor binding in tandem pose greater pandemic risk. Increasing evidence supports adding HA stability to pre-pandemic risk assessment algorithms.

SUBMITTER: Hu M 

PROVIDER: S-EPMC7326494 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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HA stabilization promotes replication and transmission of swine H1N1 gamma influenza viruses in ferrets.

Hu Meng M   Yang Guohua G   DeBeauchamp Jennifer J   Crumpton Jeri Carol JC   Kim Hyunsuh H   Li Lei L   Wan Xiu-Feng XF   Kercher Lisa L   Bowman Andrew S AS   Webster Robert G RG   Webby Richard J RJ   Russell Charles J CJ  

eLife 20200630


Pandemic influenza A viruses can emerge from swine, an intermediate host that supports adaptation of human-preferred receptor-binding specificity by the hemagglutinin (HA) surface antigen. Other HA traits necessary for pandemic potential are poorly understood. For swine influenza viruses isolated in 2009-2016, gamma-clade viruses had less stable HA proteins (activation pH 5.5-5.9) than pandemic clade (pH 5.0-5.5). Gamma-clade viruses replicated to higher levels in mammalian cells than pandemic c  ...[more]

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