In vitro Models and Molecular Tools for Investigation of Avian Metapneumovirus–Host Interactions

Infections with avian metapneumoviruses (aMPVs) pose direct and indirect health problems to domesticated poultry worldwide by predisposing to secondary infections resulting in substantial economic losses. Although this primarily impacts commercial chickens, turkeys, and ducks, inducing upper respiratory disease and drops in egg production, infection of a myriad of wild bird species also contributes to the complex global epidemiology of aMPV subtypes. The functions of aMPV viral proteins have been described, with the F protein and G protein particularly important for species tropism, facilitating sequence-based epidemiological investigations and being prime targets of the host immune response. Although <i>in vitro</i> and <i>in vivo</i> studies have provided some insights into aMPV-host interactions, knowledge regarding detailed mechanisms underlying virus entry and cell-to-cell spread as well as antagonism of innate immunity in primary cells remains limited. Some information obtained from studies with the closely related human Metapneumovirus may be applicable to aMPV but requires confirmation in the context of avian models. The establishment of reverse genetics systems for the most well-characterized aMPV subtypes A, B, and C as well as primary cell and organ culture models has enabled mechanistic investigations into virus-host interactions. In this review we provide an overview of how <i>in vitro</i> and <i>ex vivo</i> models can be utilized for aMPV isolation and propagation and concomitantly to investigate innate immune responses in a more authentic context. The construction and applications of reverse genetics systems for aMPV is also discussed with respect to facilitating investigations into the function(s) of viral proteins and identifying viral molecular determinants mediating differential virulence levels in poultry species. Collectively this provides a pathway to enable progress in key areas of aMPV research with a view to mitigating the annual disease burden resulting from intra- and interspecies aMPV infections.