Here, we investigated the role of the P-rich and FGDF motifs in the HVD of CHIKV nsP3 during virus replication in mosquito cells and infection of and transmission by in the natural CHIKV vector Ae. aegypti. Infectious cDNA clones were used to generate CHIKV variants with mutations in either the P-rich or FGDF motif(s). Here, SH2D3C is linked to infection.