Pathogenesis, Transmission, and Within-Host Evolution of Bovine-Origin Influenza D Virus in Pigs

Abstract

Whereas bovine has been demonstrated as the main reservoir of influenza D virus (IDV), this virus was first isolated in a pig and is regularly detected in some swine populations. However, the role of swine in IDV ecology, as well as the outcomes of IDV infection in pigs, is still unclear. This study aimed to provide additional information on pathogenesis, transmission, and adaptation of a bovine-origin IDV in swine. An infection and transmission study, using an IDV strain isolated following a first passage on pig of a bovine IDV, was conducted on specific pathogen-free pigs, including inoculated and direct contact pigs. Two routes of inoculation were tested, i.e., nasal and tracheal. None of the inoculated or their contact pigs showed clinical signs, but all of them shed the virus in nasal secretions and seroconverted. Virus shedding started earlier in pigs inoculated intranasally as well as in their contact pigs, compared to pigs inoculated intratracheally and associated contacts, suggesting that the viral replication occurred preferentially in the upper respiratory tract. Sequencing data brought to light a mutation on hemagglutinin-esterase-fusion protein (L118F) in the bovine IDV-derived isolate obtained after the first passage on pig. This mutation was fixed in all viral strains obtained in this study, either from inoculated or contact pigs, and was maintained over the second and third passages on swine. The L118F mutation could be linked to the adaptation of the parental bovine IDV to the swine host and might have contributed to an efficient viral multiplication and subsequent pig-to-pig transmission.