The Viral Polymerase Inhibitor 7-Deaza-2’-C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model
Fig 3
Establishment and characterization of an animal model for ZIKV infection.
Male (8–14 weeks of age) 129/Sv mice deficient in both IFN-alpha/beta (IFN-α/β) and IFN-gamma (IFN-γ) receptors (AG129) were inoculated intraperitoneally with 200 μL of different inoculums (ranging from 1×101–1×105 PFU/ml) of ZIKV. Mice were observed daily for body weight loss and the development of virus-induced disease. (A) Median day of euthanasia (MDE) is as follows: day 13.5, 15.0, 14.0, 14.5 and 18.5 pi for mice inoculated with 1×105 (n = 6), 1×104 (n = 6), 1×103 (n = 5), 1×102 (n = 2) and 1×101 (n = 4) PFU/mL, respectively. (B) Viral RNA load in brain (n = 7), spleen (n = 5), kidney (n = 5) and liver (n = 6) from ZIKV-infected mice as determined by RT-qPCR. Levels of IFN-γ (C) and IL-18 (D) were significantly increased throughout the course of infection in sera of AG129 mice (grey boxes) compared to those in sera of uninfected AG129 mice (white boxes). Statistical analysis was performed using the unpaired, two-tailed t-test. *, p<0.05.