PT  - JOURNAL ARTICLE
AU  - Pierre Bessière
AU  - Thomas Figueroa
AU  - Amelia Coggon
AU  - Charlotte Foret-Lucas
AU  - Alexandre Houffschmitt
AU  - Maxime Fusade-Boyer
AU  - Gabriel Dupré
AU  - Maxence Delverdier
AU  - Romain Volmer
TI  - The strength of the innate immune response drives the within-host competition between highly and low pathogenic avian influenza viruses
AID  - 10.1101/2021.04.06.438580
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.06.438580
4099  - http://biorxiv.org/content/early/2021/04/06/2021.04.06.438580.short
4100  - http://biorxiv.org/content/early/2021/04/06/2021.04.06.438580.full
AB  - Highly pathogenic avian influenza viruses (HPAIV) emerge from low pathogenic avian influenza viruses (LPAIV) through the introduction of basic amino acids at the hemagglutinin (HA) cleavage site. Following viral evolution, the newly formed HPAIV likely represents a minority variant within the index host, predominantly infected with the LPAIV precursor. Using reverse-genetics engineered H5N8 viruses differing solely at the HA cleavage, we tested the hypothesis that the interaction between the minority HPAIV and the majority LPAIV could modulate the risk of HPAIV emergence and that the nature of the interaction could depend on the host species. In chickens, we observed that the H5N8LP increased H5N8HP replication and pathogenesis. By contrast, the H5N8LP antagonized H5N8HP replication and pathogenesis in ducks. Ducks mounted a more potent antiviral innate immune response than chickens against the H5N8LP, which correlated with H5N8HP inhibition. Our results provide evidence that HPAIV may be more likely to emerge in chickens than in ducks because of differences in the host response to HPAIV and LPAIV co-infections.