Pathogenicity of a chicken-origin cluster 3 isolate of Tembusu virus in Pekin ducklings and Kunming mice

Tembusu virus (TMUV) is genetically classified into three clusters. To date, information relating to the pathogenicity of TMUV cluster 3 in ducks is limited; whether TMUV cluster 3 has the potential to induce disease in mice remains unclear. Here, we evaluated the pathogenicity of a chicken-origin TMUV cluster 3 strain G (TMUV/G) in 5-day-old Pekin duck and 3-week-old Kunming mouse models by comparing with TMUV cluster 2.1 strain H (TMUV/H). TMUV/G caused neurological diseases in both ducklings and mice. Whereas TMUV/G was less virulent than TMUV/H, with more mild clinical signs and microscopic lesions and significantly lower morbidity. TMUV/G caused 10 % mortality in ducklings and failed to cause mortality in mice, in sharp contrast with 90 % mortality in ducklings and 60 % mortality in mice induced by TMUV/H. Further analysis with the mouse model revealed that TMUV/G replicated to lower levels in the central nervous system, and induced lower IFN-β, IL-6, TNF-α, and Viperin responses in the infected cerebrum. Compared with TMUV/H, TMUV/G contained a number of mutations throughout the genome and had a reduced replication efficiency in cultured hippocampal neuronal (HT22) cells. Together these findings suggest that TMUV/G displays markedly lower virulence in Pekin ducklings and Kunming mice relative to TMUV/H, indicating that different virus-host interactions exist between cluster 3 and 2.1 TMUVs. The present work contributes to the understanding of virulence phenotype of TMUV cluster 3, and will stimulate further studies on the mechanism for substantial virulence attenuation of TMUV cluster 3 relative to TMUV cluster 2.1.