Abstract Canine distemper virus (CDV), a member of the genus Morbillivirus within the family Paramyxoviridae, is a highly contagious pathogen affecting a wide range of carnivores. Although traditionally considered species-specific, increasing evidence of CDV infection across diverse hosts, including non-human primates, raises concerns about its zoonotic potential. This review evaluates the virology, host range expansion, molecular determinants of host specificity, and experimental evidence of human susceptibility within the time frame of 2000–2026. While no confirmed human infections have been reported, molecular studies demonstrate that CDV can adapt to utilize human cellular receptors, suggesting a plausible risk for future spillover. A One Health approach is essential for monitoring and mitigating this emerging threat. 1. Introduction Emerging infectious diseases frequently arise from animal reservoirs, particularly RNA viruses with high mutation rates. Members of the genus Morbillivirus, including measles virus, are known for their high transmissibility and pathogenicity in humans. Canine distemper virus (CDV) is closely related to measles virus and shares structural and functional similarities, including receptor usage and immune evasion strategies (Beineke et al., 2015). Initially described in dogs, CDV has expanded its host range to include numerous wildlife species, raising concerns about interspecies transmission and zoonotic potential. 2. Virology and Genome Organization CDV is an enveloped, negative-sense single-stranded RNA virus with a genome of approximately 15.7 kb encoding six structural proteins: N (nucleocapsid) P (phosphoprotein) M (matrix protein) F (fusion protein) H (hemagglutinin protein) L (RNA-dependent RNA polymerase) The hemagglutinin (H) protein is critical for receptor binding and host specificity, while the fusion (F) protein mediates viral entry (Rendon-Marin et al., 2019). 3. Host Range and Epidemiology CDV has one of the broadest host ranges among RNA viruses, infecting: Domestic dogs Wild carnivores (foxes, wolves, lions) Marine mammals (seals, dolphins) Non-human primates Outbreaks have been reported worldwide, often causing significant mortality in wildlife populations (Rendon-Marin et al., 2019). Transmission occurs via: Aerosolized respiratory droplets Direct contact with bodily fluids The expanding host range highlights CDV’s adaptability and evolutionary potential. 4. Molecular Determinants of Host Specificity CDV primarily uses two host receptors: SLAM (Signaling Lymphocyte Activation Molecule; CD150) Expressed on immune cells Determines species susceptibility Nectin-4 Expressed on epithelial cells Facilitates viral spread Mutations in the H gene enable CDV to bind receptors from different species. Experimental studies show that only a few amino acid substitutions are required for CDV to efficiently use human SLAM receptors (Bieringer et al., 2013). 5. Evidence of Cross-Species Transmission 5.1 Infection in Non-Human Primates A key milestone in assessing zoonotic risk is the infection of species closely related to humans. CDV has caused outbreaks in cynomolgus macaques and other primates Clinical disease resembles human measles Demonstrates ability to overcome species barriers These findings strongly suggest that CDV is not restricted to carnivores (Qiu et al., 2011). 5.2 Experimental Adaptation to Human Cells Laboratory studies have shown: CDV can infect human epithelial and immune cells under experimental conditions Adapted strains can utilize human SLAM and nectin-4 receptors Minimal genetic changes are required for host switching (Bieringer et al., 2013; Rendon-Marin et al., 2019) 5.3 Lack of Confirmed Human Cases Despite these findings: No confirmed natural human infections have been reported Possible explanation: cross-protective immunity from measles vaccination Serological evidence in humans remains inconclusive 6. Role of Measles Immunity A critical factor limiting CDV zoonosis is immunity induced by the measles virus: Measles and CDV share antigenic similarities Neutralizing antibodies against measles may partially protect against CDV Declining measles vaccination coverage could increase susceptibility (Beineke et al., 2015) 7. Mechanisms of Potential Spillover Potential zoonotic transmission of CDV would likely involve: Mutation in H protein Enhanced binding to human SLAM receptors Adaptation in fusion protein Improved viral entry into human cells Immune escape Avoidance of measles-derived immunity High exposure scenarios Wildlife-human interfaces Domestic animal contact 8. Public Health Implications Although CDV is not currently a human pathogen, several features are concerning: Broad host range Ability to infect primates Minimal mutations required for human adaptation Similarity to measles virus If CDV adapts to humans, it could potentially cause: Respiratory disease Immunosuppression Neurological complications 9. One Health Perspective A One Health framework is essential for monitoring CDV: Veterinary surveillance: domestic and wild animals Human surveillance: high-risk populations Vaccination strategies: maintaining measles immunity Integration across disciplines can help detect early warning signs of zoonotic emergence. 10. Limitations and Research Gaps Key gaps include: Lack of human challenge or exposure studies Limited understanding of receptor adaptation in vivo Insufficient genomic surveillance in wildlife Unknown potential for human-to-human transmission 11. Conclusion Between 2000 and 2026, canine distemper virus has demonstrated significant host expansion and molecular adaptability, positioning it as a potential zoonotic pathogen. While no human infections have been confirmed, experimental evidence indicates that CDV can utilize human receptors and infect primate hosts. The presence of cross-protective measles immunity may currently limit its emergence. However, declining vaccination rates and ongoing viral evolution highlight the need for continued surveillance and preparedness. Time Frame Covered 2000 – 2026(Focus on host expansion, molecular adaptation, and zoonotic risk) References (APA Style) Beineke, A., Baumgärtner, W., & Wohlsein, P. (2015). Cross-species transmission of canine distemper virus. Veterinary Pathology, 52(1), 24–34. Bieringer, M., Han, J. W., Kendl, S., Khosravi, M., Plattet, P., & Schneider-Schaulies, J. (2013). Experimental adaptation of canine distemper virus to human receptors. PLoS ONE, 8(3), e57488. 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Zahid Hussain (Mon,) studied this question.