Figure 3.
Characterization of the C7 mutant with adaptive mutations (C7a). (a) Comparison of specific infectivity between C7 and C7a (with adaptive prM E21K and NS2B E27G mutations). Upper-left panel outlines the experimental procedures. Infectious cDNA clone-derived C7 and C7a RNAs were transfected into BHK-HA-C cells. Transfected cells were serially diluted and seeded onto BHK-HA-C cell monolayers. Focus-forming units were detected by immunostaining on day 4 post-transfection. PFU/μg RNA values were calculated and presented in the upperright panel. The lower panel shows the morphology of the foci after immunostaining. Statistically significant differences were determined using a t-test. (b) IFA of RNA-transfected Vero, BHK-21, and BHK-HA-C cells. C7a RNAs (containing the C7 deletion plus prM E21K and NS2B E27G mutations) were electroporated into BHK-21 or BHK-HA-C cells. The viral E protein expression was monitored by IFA. (c) Virus titers in supernatants on day 4 p.t. determined by focus-forming assay. (d) Focus morphology. C7a/t viruses were harvested from the C7a RNA-transfected BHK-HA-C cells on day 4 post-transfection. Focus morphology of C7a/t virus was determined on Vero, BHK-21, and BHK-HA-C cells. (e) Viral replication kinetics. BHK-21 or Vero cells were infected with C7a/t or WT ZIKV at an MOI of 0.5. Virus titers were measured by focus-forming assay on BHK-HA-C cells. Statistical significance was determined using multiple t-test. (f) IFA for monitoring the spread of WT ZIKV infection. (g) IFA for monitoring the spread of C7a/t virus infection. Cells were infected with WT or C7a/t virus (MOI 0.25). Viral E protein expressing cells were quantified by IFA using 4G2 antibody. Percentages of E-positive cells are presented. CPE, viral infection-mediated cytopathic effect; +, mild; ++, moderate; +++, severe. (h) Western blot analysis of C7a/t virus. Supernatants from replicon RNA-transfected BHK-HA-C cells (day 4 p.t.), WT RNA-transfected Vero cells (day 4 p.t.), and C7a RNA-transfected BHK-HA-C cells (day 4 p.t.) were analyzed for viral proteins (HA-C, C, M, E, and NS1) using Western blotting.
