Figure 7.
In vivo and in vitro characterization of DENV1-NS1-D2Y98P and DENV1-prME-D2Y98P chimeric viruses. (A and B) DENV1-NS1-D2Y98P (A) or DENV1-prME-D2Y98P (B) chimeric strains consist of NS1 (A) or (B) coding region from DENV1 strain (blue) cloned into the backbone of D2Y98P strain (red). AG129 mice were infected s.c. with 106 PFU of D2Y98P, DENV1, DENV1-NS1-D2Y98P, or DENV1-prME-D2Y98P. Mice (n = 8) were monitored daily upon challenge. (C–F) Kaplan–Meier survival curves (C and D) and clinical scores (E and F) are shown. (G) Viremia titers were measured at days 1, 3, and 5 p.i. (n = 4). (H and I) In vitro virus titer in Vero cells infected with respective viruses. The viral kinetic curves were compared and analyzed by linear regression, which takes into consideration the slope and Y-intercept. (J) TNF-α, IL-6, and IL-10 systemic levels were measured at day 5 p.i. (n = 4–5). Data are representative of at least two independent experiments. Data between WT and chimeric viruses were compared and analyzed by nonparametric Mann–Whitney U test. *, P < 0.05; **, P < 0.01; ns, not significant. Results were expressed as averages ± SD (H and I).