Figure 1.

The genotype I of DENV-3 (MG20) isolate is neurovirulent. Nos2^−/− mice are resistant to infection, while Ifng^−/− and WT mice are susceptible to infection. Mice were intracranially (i.c.) inoculated with DENV and monitored daily until 15 d.p.i. Mice inoculated with uninfected C6/36 cell supernatants were used as controls (n = 5 for all the groups). (A) 4 × 10³ to 4 × 10 pfu of DENV-3 (MG20, Pi76 or MG21). * P < 0.05, ** P < 0.01 when comparing 4 × 10² DENV-3 (MG20) and 4 × 10² DENV-3 (MG21) or 4 × 10³ DENV-3 (MG20) and 4 × 10³ DENV-3 (MG21) with 4 × 10 DENV-3 (MG20), 4 × 10 DENV-3 (MG21) or the three different doses used in the DENV-3 (Pi76), or the cell supernatant. (B) 4 × 10² pfu of DENV-3 (MG20) or DENV-1 (Hotta, 1951). *P <0.05, when comparing DENV-1 or DENV-3 (MG20)-infected animals to the supernatant-inoculated animals. (C) 4 × 10² pfu of DENV-3 (MG20) in C57BL/6 (WT), Ifng^−/− and Nos2^−/− mice. *P < 0.05 and P < 0.001, when comparing Nos2^−/− mice with WT mice or with Ifng^−/− mice (D) Body weight was expressed as a percentage of the initial weight of the animal. Survival curves were statistically analyzed using the Kaplan-Meier method followed by log-rank tests. The results are representative of two similar and independent experiments.