Lineage-dependent differences in the disease progression of Zika virus infection in type-I interferon receptor knockout (A129) mice

Zika virus (ZIKV) falls into two lineages: African (ZIKV(AF)) and Asian (ZIKV(AS)). These lineages have not been tested comprehensively in parallel for disease progression using an animal model system. Here, using the established type-I interferon receptor knockout (A129) mouse model, it is first demonstrated that ZIKV(AF) causes lethal infection, with different kinetics of disease manifestations according to the challenge dose. Animals challenged with a low dose of 10 plaque-forming units (pfu) developed more neurological symptoms than those challenged with 5-log higher doses. By contrast, animals challenged with ZIKV(AS) displayed no clinical signs or mortality, even at doses of 10(6) pfu. However, viral RNA was detected in the tissues of animals infected with ZIKV strains from both lineages and similar histological changes were observed. The present study highlights strain specific virulence differences between the African and Asian lineages in a ZIKV mouse model.