Orthomyxoviruses Beyond Influenza A and B: A One Health Perspective on the Emerging Roles of Influenza C and D Viruses

Influenza C and D viruses are emerging but understudied members of the Orthomyxoviridae family with increasing relevance to human, animal, and environmental health. This review examines their virology, ecology, host range, and transmission through a One Health lens. Influenza C remains an endemic human pathogen capable of infecting several mammals, while recent detections in cattle highlight previously unrecognized cross-species exchange. Influenza D has become globally established in cattle and multiple livestock species, with high seroprevalence in bovines and frequent human exposure among cattle workers despite no confirmed illness. Both viruses rely on a single hemagglutinin-esterase-fusion glycoprotein and use 9-O-acetylated sialic acids, features that distinguish them from influenza A and B and indicate unique evolutionary pathways. Their wide host ranges, environmental stability, and undetected circulation demonstrate critical gaps in current surveillance. Strengthening integrated human and animal monitoring and expanding research inclusion of influenza C and D are essential public health priorities.