Lineage-dependent differences of Zika virus infection in a susceptible mouse model are associated with different profiles of cytokines, chemokines, growth factors and acute phase proteins

Abstract

Zika virus (ZIKV) is phylogenetically divided into two lineages comprising African (ZIKV^AF) and Asian (ZIKV^AS) genotypes. In the type-I interferon receptor deficient mouse model, ZIKV^AF causes severe disease with all mice meeting humane endpoints with doses as low as 10 plaque-forming units (pfu) whereas a much milder infection is seen after challenge with ZIKV^AS, including with doses as high as 10⁶ pfu. Using this mouse model, the elucidation of cytokine, chemokine, growth factor and acute phase protein responses over the course of infection were studied to determine whether these analytes contributed to the stark difference in clinical outcome. Results demonstrated some significant differences, with the ZIKV^AF infection being associated with increases in a higher number of biomarkers than ZIKV^AS. When low (10 pfu) and high (10⁶ pfu) challenge doses were compared, animals given the lower virus inoculum showed a wider range of responses, indicating a different disease progression compared to those challenged with high doses. These results aid with elucidating the different outcomes with the two lineages of ZIKV and with future work to assess pathogenicity of virus infection.

Keywords: Acute phase proteins; Chemokine; Cytokine; Growth factors; Pathogenicity; Zika virus.