Abstract Canine influenza viruses (CIVs), particularly subtypes H3N2 and H3N8, are emerging respiratory pathogens in dogs with increasing global distribution. Originating from avian and equine influenza viruses, these viruses demonstrate significant genetic plasticity, enabling cross-species transmission and reassortment. This review examines the zoonotic potential of CIVs within the time frame of 2004–2026, focusing on molecular evolution, host adaptation, and experimental evidence of human susceptibility. Although no confirmed human infections have been reported, studies indicate limited human immunity, compatibility with human influenza strains, and adaptation to human respiratory cells. These findings underscore the importance of surveillance and pandemic preparedness under a One Health framework. 1. Introduction Influenza A viruses (IAVs) are segmented, negative-sense RNA viruses with a well-documented capacity for interspecies transmission and pandemic emergence. Historical pandemics, including the 2009 H1N1 outbreak, highlight the role of animal reservoirs in generating novel human pathogens. Canine influenza viruses (CIVs) are relatively recent additions to the IAV host range. Two major subtypes circulate globally: H3N8 (equine-origin) H3N2 (avian-origin) Since their emergence, CIVs have raised concerns due to their ability to infect mammals in close contact with humans (Parrish ). 2. Origin and Evolution of CIVs 2.1 H3N8 Canine Influenza Virus H3N8 CIV emerged around 2002 through host-range shift from equine influenza virus and became enzootic in dogs (He et al., 2019; ). First outbreak: 2004, Florida (greyhounds) Evolution: multiple clades via reassortment Adaptation: efficient dog-to-dog transmission 2.2 H3N2 Canine Influenza Virus H3N2 CIV originated from avian influenza viruses and was first detected in East Asia around 2006–2007 (). Spread: Asia → North America Host range: dogs, cats, and other mammals Higher genetic diversity than H3N8 3. Molecular Characteristics and Host Adaptation CIVs possess eight segmented RNA genomes, facilitating reassortment with other influenza viruses. Key features include: Hemagglutinin (HA): receptor binding and host specificity Neuraminidase (NA): viral release Polymerase complex (PB2, PB1, PA): replication efficiency Experimental studies show that CIVs can acquire mutations enhancing replication in human cells. For example, H3N8 CIV developed mutations in HA and NA that increased growth in human respiratory epithelial cells (Sekine et al., 2024; ). 4. Epidemiology in Canine Populations CIVs are highly contagious among dogs, especially in: Kennels Shelters Veterinary clinics Transmission occurs via: Respiratory droplets Direct contact Contaminated surfaces Global spread is facilitated by pet movement and close human-dog interaction (CDC, 2024; ). 5. Evidence of Zoonotic Potential 5.1 Lack of Confirmed Human Infections To date: No confirmed human cases of CIV infection have been reported worldwide Epidemiological studies show no serological evidence of infection in exposed humans (Krueger et al., 2014; ) Public health agencies classify CIV risk as low (CDC, 2024; ) 5.2 Experimental and Molecular Evidence Despite the lack of confirmed cases, several findings raise concern: 1. Limited Human Immunity H3N2 CIV is antigenically distinct from human influenza strains, suggesting minimal preexisting immunity in humans (). 2. Reassortment with Human Viruses CIV-H3N2 can reassort with pandemic H1N1 (2009) strains, producing viruses with enhanced replication and transmissibility in animal models (). 3. Adaptation to Human Cells H3N8 CIV can evolve mutations enabling efficient replication in human respiratory cells (). 4. Dogs as “Mixing Vessels” Dogs can be co-infected with: Avian influenza viruses Human influenza viruses Swine influenza viruses This creates opportunities for reassortment and emergence of novel strains (). 6. Mechanisms of Potential Spillover Zoonotic transmission of CIVs would likely involve: Receptor binding adaptation Shift from avian-type (α2,3) to human-type (α2,6) sialic acid receptors Genetic reassortment Exchange of gene segments with human influenza viruses Close human-dog contact Companion animals increase exposure risk Intermediate adaptation Dogs acting as bridging hosts between birds and humans 7. Public Health Implications Although current risk is low, CIVs possess characteristics associated with pandemic potential: Segmented genome enabling reassortment Ability to infect multiple species High mutation rate Global distribution in companion animals Importantly, influenza viruses have historically emerged through animal-to-human transmission, emphasizing the need for vigilance. 8. One Health Perspective A One Health approach is critical to managing CIV risks: Veterinary surveillance: monitoring canine populations Human health surveillance: serological studies in exposed populations Environmental monitoring: tracking virus circulation Integrated surveillance can help detect early spillover events and prevent outbreaks. 9. Limitations and Research Gaps Key gaps include: Lack of longitudinal human exposure studies Limited data on receptor binding specificity in humans Unclear efficiency of human-to-human transmission Insufficient genomic surveillance in developing countries 10. Conclusion Between 2004 and 2026, canine influenza viruses (H3N2 and H3N8) have evolved into globally distributed pathogens with demonstrated zoonotic potential but no confirmed human infections. Experimental evidence indicates that these viruses can adapt to human cells, reassort with human influenza strains, and evade preexisting immunity. While the current public health risk remains low, the evolutionary dynamics of CIVs justify continued surveillance and preparedness efforts. Dogs may serve as critical intermediates in the emergence of future influenza pandemics. Time Frame Covered 2004 – 2026(Focus on emergence, evolution, zoonotic risk, and experimental studies) References (APA Style) Centers for Disease Control and Prevention. (2024). About dog flu. He, W., Li, G., Wang, R., Shi, W., Li, K., Wang, S., & Su, S. (2019). Host-range shift of H3N8 canine influenza virus. Veterinary Research, 50, 87. Krueger, W. S., Heil, G. L., Yoon, K. J., & Gray, G. C. (2014). No evidence for zoonotic transmission of H3N8 canine influenza virus. Influenza and Other Respiratory Viruses, 8(1), 99–106. Parrish, C. R., & Voorhees, I. E. H. (2019). H3N8 and H3N2 canine influenza viruses. Veterinary Clinics of North America: Small Animal Practice, 49(4), 643–649. Sekine, W., Kamiki, H., Ishida, H., Matsugo, H., Ohira, K., Li, K., & Horimoto, T. (2024). Adaptation potential of H3N8 canine influenza virus in human respiratory cells. Scientific Reports, 14, 18750. Vlasova, A. N., et al. (2017). Zoonotic risk, pathogenesis, and transmission of avian-origin H3N2 canine influenza virus. Journal of Virology.
Zahid Hussain (Sun,) studied this question.