Determining the replication kinetics and cellular tropism of the ruminant-associated Influenza D virus on primary human airway epithelial cells

Holwerda, Melle; Laloli, Laura; Stürmer, Isabel; Portmann, Jasmine; Stalder, Hanspeter; Dijkman, Ronald

Influenza viruses are notorious pathogens that frequently cross the species barrier with often severe consequences for both animal and human health. In 2011, a novel member of the Orthomyxoviridae family, Influenza D virus (IDV), was identified in the respiratory tract of diseased swine. Epidemiological surveys revealed that IDV is distributed worldwide among livestock and that IDV-directed antibodies are detected in humans with occupational exposure to livestock. To identify the transmission capability of IDV to humans, we determined the viral replication kinetics and cell tropism using an in vitro respiratory epithelium model of humans. The inoculation of IDV revealed efficient replication kinetics and apical progeny virus release at different body temperatures. Intriguingly, the replication characteristics of IDV revealed many similarities to the human-associated Influenza C virus, including the cell tropism preference for ciliated cells. Collectively, these results might indicate why IDV-directed antibodies are detected among humans with occupational exposure to livestock. One-sentence summary of the conclusion We show that the ruminant-associated Influenza D virus has direct transmission capability to humans.