Location: Exotic & Emerging Avian Viral Diseases Research
Project Number: 6040-32000-081-013-A
Project Type: Cooperative Agreement
Start Date: Apr 1, 2021
End Date: Feb 28, 2026
Objective:
This work describes a series of experiments designed to assess the effects of innate and adaptive immunity on evolution of AIV, in vitro, and in vivo. The unifying approach is to examine how virus strains from the H5NX (especially clade 2.3.4.4), H7N9 and H9N2 lineages, which pose the greatest current risk to both animals and humans, change at the quasi species level under various selective pressures: host switches, host immunity and virus competition. We will use in vitro and in vivo systems as complementary approaches that allow virus evolution to be interrogated at relatively high throughput at tissue level and at lower throughput but whole organism level. The resulting information will be used to inform and parameterize the models generated by collaborators.
This work describes a series of experiments designed to assess the effects of innate and adaptive immunity on evolution of AIV, in vitro, and in vivo. The unifying approach is to examine how virus strains from the H5NX (especially clade 2.3.4.4), H7N9 and H9N2 lineages, which pose the greatest current risk to both animals and humans, change at the quasi species level under various selective pressures: host switches, host immunity and virus competition. We will use in vitro and in vivo systems as complementary approaches that allow virus evolution to be interrogated at relatively high throughput at tissue level and at lower throughput but whole organism level. The resulting information will be used to inform and parameterize the models generated by collaborators.
Approach:
The roles of host-related factors and innate immunity on virus evolution will be determined in vitro and in vivo through two approaches: (1) Using chicken, quail, and duck embryonic fibroblasts and tracheal organ cultures as models of domestic and wild bird hosts; secondly, in vivo passage of viruses through mallard ducks and Chinese goose species to predict evolution in natural hosts; thirdly, viral evolution and transmission dynamics of avian influenza virus (AIV) infection in Japanese quail as an indicator species of potential to jump into mammalian hosts (because of their expression of salicylic acid (SA) receptors for both avian (a-2,3) and mammalian (a2,6) influenza viruses.
(2) The dynamics of virus subtype and host species will be determined in vivo through two approaches; firstly, by testing suboptimal immunity in vaccinated chickens (H5/H7 vaccines) and mallard ducks (live low pathogenic avian influenza (LPAI) pre-exposure) followed by highly pathogenic avian influenza (HPAI) challenge; secondly, by passage of LPAIV H7 and H9 in naïve quail that contain SA receptors for both avian and mammalian avian influenza virus.
