Exploration of the Pathogenicity and Inflammatory Mechanism of Wuxiang Virus: A Newly Identified Phlebovirus

ABSTRACT WUXV is phlebovirus transmitted by sandflies, which can cause death in suckling mice and infect humans and chickens. However, little is known about the pathogenicity and pathogenic mechanisms of animals. Therefore, BALB/c WT mice and BALB/c nude mice were infected with WUXV. No fatal diseases occurred except for weight loss among the BALB/c WT mice, while BALB/c nude mice observed significant neurological symptoms and death. The virus nucleic acid was detected in the organs and blood of both mice. The blood routine showed a significant increase in RDW, and IgM, IgG, and neutralizing antibodies were detected in the serum of the BALB/c WT mice, which were significantly higher than those of BALB/c nude mice. The inflammatory factors in tissues, and pathological section results, indicate that WUXV caused severe inflammatory reactions. In addition, we found that WUXV activates the inflammatory pathway by activating TLR5 and TLR9. Inhibition of TLR5 and TLR9 can eliminate the activation of NF‐κb and downstream inflammatory factors. In summary, we systematically studied the pathogenicity and pathogenesis of WUXV infection in mice with different immune states, and found that TLR5 in mammalian cells can serve as RNA sensor, expanding our understanding of the virus.