Dual miRNA Targeting Restricts Host Range and Attenuates Neurovirulence of Flaviviruses
Fig 4
Effect of combined mir-184 and mir-275 co-targeting of DEN4 genome in the 3’NCR on virus fitness in A. aegypti and A. albopictus.
A. aegypti (A and C) and A. albopictus (B and D) were orally infected with blood meals (BM) containing 7.1 to 7.4 log10 pfu/ml of recombinant D4 or D4-275-184 virus, respectively, and processed at 14 dpi. (A and B) Each point represents virus titer in individual mosquito (n = 18 for A. aegypti exposed to D4, and n = 24 mosquitoes for each other virus). Horizontal line represents an average titer for all mosquitoes. The dashed line indicates the limit of the assay detection [0.2 log10 pfu/mosquito]. P-values comparing mean titers of D4 and miRNA targeted viruses were calculated using unpaired one-tailed Student's t-test and adjusted using Bonferroni correction method to account for multiple comparisons. (C and D) Percentage of mosquitoes that became infected (blue) or developed a disseminated infection (orange) with each virus. Differences in infection and dissemination frequencies were compared between D4 and miRNA targeted viruses using one-tailed Fisher’s exact test. P-values were adjusted using Bonferroni correction method to account for multiple comparisons.