Experimental Infection of Rats with Influenza A Viruses: Implications for Murine Rodents in Influenza A Virus Ecology

Rattus norvegicus (brown rat), a widely distributed rodent and common biomedical model, serves as a source of many zoonotic pathogens but is not traditionally recognized as a host for influenza A virus (IAV). To assess their susceptibility, we intranasally inoculated Sprague-Dawley rats with different IAV subtypes (H5Nx, H7N9, H9N2, H10N8 and the 2009 pandemic H1N1). All strains productively infected the rats, inducing seroconversion and mild weight reduction without overt clinical signs. Despite differences in replication, all viruses caused significant lung injury with a preferential upper respiratory tract tropism. Investigation of receptor distribution revealed α2,3-linked sialic acid (SA) dominance in the nasal turbinates and trachea, whereas α2,6-linked SA predominated in the lungs, although both receptors coexisted throughout the respiratory tract. This dual receptor expression aligns with the observed tissue-specific replication patterns and broad viral infectivity. Our results demonstrate that the rat is a permissive host for multiple IAV subtypes, challenging its exclusion from the IAV ecology. The asymptomatic yet pathogenic nature of infection, coupled with the global synanthropy of rats, underscores their potential role as cryptic reservoirs in viral maintenance and transmission. These findings highlight the need for expanded surveillance of rodents in influenza ecology to mitigate zoonotic risks.