Mammalian adaptation and zoonotic risk of influenza A viruses in companion animals.

IMPORTANCE: Since the early 2000s, companion animals emerged as unexpected players in influenza A virus ecology. Canine influenza viruses and the increasing detection of highly pathogenic avian influenza viruses in cats have raised concerns about their potential role as intermediate hosts for pandemic emergence. Their unique position at human-animal interface creates unprecedented opportunities for viral evolution and bidirectional transmission between humans and animals. OBSERVATIONS: This review examined the transmission pathways and molecular adaptations of influenza A virus in companion animals. Cats primarily acquire infections through alimentary routes, including consumption of raw poultry and unpasteurized milk, as well as environmental exposure through hunting. Dogs transmit influenza viruses via respiratory droplets in high-density settings such as shelters and kennels. Canine influenza viruses demonstrate successful mammalian adaptation through accumulated mutations across multiple viral proteins, particularly in polymerase and hemagglutinin genes, enabling sustained dog-to-dog transmission. Feline isolates consistently exhibit mammalian adaptive mutations across geographically disparate outbreaks. Several molecular changes appear convergently in both species, suggesting shared evolutionary pressures at companion animal-human interface. CONCLUSIONS AND RELEVANCE: Despite molecular evidence of active viral evolution, companion animals currently pose a limited pandemic risk owing to no sustained zoonotic transmission chains. Critical knowledge gaps remain regarding subclinical infection frequency, natural transmission efficiency, and host genetic factors that influence susceptibility. Surveillance should prioritize high-risk interfaces, including raw pet food supply chains and veterinary facilities, while maintaining the perspective of actual versus theoretical risks. Understanding companion animal influenza virus dynamics is essential for comprehensive pandemic preparedness strategies.