Identification of prevalent Feline Calicivirus strains and novel antiviral efficacy of CpG49 stimulus in Feline Calicivirus-infected cats.

Feline calicivirus (FCV) is a highly mutable and prevalent virus causing significant suffering in cats and currently lacking effective cures, while FCV studies mainly focus on prevention. To obtain an active therapeutic against FCV, we established a reliable FCV infection model using the prevalent FCV strain (FG24-1) isolated from clinical samples and evaluated the therapeutic effect of TLR9 agonist CpG49 (a CpG plasmid with well-immunostimulatory capacity) on this model. Our results showed that CpG49 elicited strong Th1-biased interferon (I and II) responses, thereby significantly inhibiting FCV replication both in vitro and in vivo. Notably, CpG49 significantly reduced serum levels of the inflammatory marker fSAA (maximum reduction: 40.38 %) while upregulating IFN-γ (maximum increase: 2.14-fold), suggesting its potential to alleviate excessive inflammatory damage and provoke a more balanced immunity. These immunostimulatory effects of CpG49 lessened clinical symptoms, accelerated recovery (high-dose CpG49 group showed 3-day shorter oral inflammation recovery time, 2-day less fever duration, and faster weight recovery), and reduced viral shedding (53.4 % lower on day 6 and 97.4 % lower on day 9 after treatment) in FCV-infected cats. This study supports CpG49's potential as a promising and safe therapeutic agent against FCV, providing a new direction for developing cost-effective FCV therapeutics.