Pathobiology and innate immune responses of gallinaceous poultry to clade 2.3.4.4A H5Nx highly pathogenic avian influenza virus infection

Abstract

In the 2014–2015 Eurasian lineage clade 2.3.4.4A H5 highly pathogenic avian infuenza (HPAI) outbreak in the U.S., backyard focks with minor gallinaceous poultry and large commercial poultry (chickens and turkeys) operations were afected. The pathogenesis of the frst H5N8 and reassortant H5N2 clade 2.3.4.4A HPAI U.S. isolates was investi‑ gated in six gallinaceous species: chickens, Japanese quail, Bobwhite quail, Pearl guinea fowl, Chukar partridges, and Ring-necked pheasants. Both viruses caused 80–100% mortality in all species, except for H5N2 virus that caused 60% mortality in chickens. The surviving challenged birds remained uninfected based on lack of clinical disease and lack of seroconversion. Among the infected birds, chickens and Japanese quail in early clinical stages (asymptomatic and listless) lacked histopathologic fndings. In contrast, birds of all species in later clinical stages (moribund and dead) had histopathologic lesions and systemic virus replication consistent with HPAI virus infection in gallinaceous poultry. These birds had widespread multifocal areas of necrosis, sometimes with heterophilic or lymphoplasmacytic infam‑ matory infltrate, and viral antigen in parenchymal cells of most tissues. In general, lesions and antigen distribution were similar regardless of virus and species. However, endotheliotropism was the most striking diference among species, with only Pearl guinea fowl showing widespread replication of both viruses in endothelial cells of most tis‑ sues. The expression of IFN-γ and IL-10 in Japanese quail, and IL-6 in chickens, were up-regulated in later clinical stages compared to asymptomatic birds.