Functional divergence of feline calicivirus genotypes shapes virulence and antigenic diversity.

Feline calicivirus (FCV) is a major respiratory pathogen in felids, which brings an economic burden to the world, such as increasing veterinary costs, strict epidemic management, and increasing animal mortality. The poor feeding management in China makes the highly virulent systemic feline calicivirus (VS-FCV) spread rapidly, thus becoming a public health problem. We examined the factors driving FCV virulence enhancement. We combined global phylogenetic reconstruction with experimental validation. Bayesian analysis classified existing FCV isolates into two genotypes: GI and GII. GII predominates in recent Asian outbreaks. This lineage demonstrates superior host adaptability, likely due to specific codon usage patterns and VP1 structural evolution. We compared the pathogenicity of GI (WH0531) and GII (WX9) in vivo. The GII isolate WX9 caused higher mortality and wider tissue tropism than GI WH0531. Immune assays confirmed restricted cross-protection between the two genotypes. Antigenic variation restricts current prevention strategies. Genotype determines FCV pathogenicity and shapes the evolutionary history of the virus. A diagram depicting the relationship between molecular evolution and clinical phenotypes was drawn. This study lays a solid scientific foundation for the development of the next - generation broad - spectrum vaccines to neutralize the increasingly lethal feline diseases.