Identification and Pathogenicity Analysis of Feline Calicivirus in Shanghai and Guangdong, China

Feline calicivirus (FCV; <i>Caliciviridae</i>) is a highly contagious RNA virus that causes upper respiratory tract infections and intestinal symptoms in cats. In 2023 and 2024, in Shanghai (SH), China, we collected oral swab samples from 189 domestic cats exhibiting symptoms of upper respiratory tract disease (URTD), to test for five designated respiratory pathogens. Among the 111 cats testing positive for these pathogens, the FCV-positivity rate was 52% (58/111). Six FCV strains (three from SH and three from Guangdong [GD]) were successfully isolated from respiratory specimens from domestic cats. Whole genome sequencing and phylogenetic analyses revealed that these strains exhibited the GII FCV genotype, suggesting that this is the dominant genotype in Asia. Within the first 36 h postinfection, the GD strains exhibited faster growth and higher replication titers than the SH strains. The GD23-02 genotype (GD) and SH23-13 genotype (SH) exhibited intriguing amino acid variation in the VP1 E-region. We therefore selected these strains for challenge experiments. Although both strains caused oral-ulcer symptoms, they presented distinct disease progression and clinical manifestations; SH23-13 exhibited traits typical of virulent systemic disease (VSD), whereas GD23-02 predominantly exhibited symptoms of oral respiratory disease (ORD). Notably, both strains consistently induced severe diarrhea and intestinal damage, demonstrating the harmful effects of FCV on intestinal health. GD23-02 exhibited broad-spectrum neutralization capabilities, with antibody titers of 1:168 against the F9 vaccine GI strain and 1:2521 against the SH23-13 GII strain, making this a promising candidate for future vaccine formulation. These findings reveal the genetic diversity and complex pathogenicity of FCV isolates and elucidate the associations between FCV strains and intestinal disease. We recommend incorporating FCV testing into future diagnostic evaluation of feline diarrhea. This testing will be essential in elucidating the tissue specificity of FCV and potential escalation in its virulence.