Fig. 4.

Methacycline reduces Zika virus (ZIKV) infection in a mouse model. (A) Overview of in vivo protocol. Mice were treated with methacycline daily from birth, infected with Zika virus at postnatal day 1 (PND1), and killed at PND12. (B) Zika virus-infected mice gain weight at a slower rate. Methacycline treatment improved (C) trunk control, (D and E) muscle strength, and (F) balance. Methacycline reduced (G) Zika virus RNA levels, visualized using a Zika virus-specific probe that targets the 219–5443 fragment of the consensus sequence and quantified by qRT-PCR (SI Appendix, Fig. S8A), and Zika virus protein levels, visualized using (H) chromogenic immunohistochemistry and (I) fluorescent immunohistochemistry images and quantified with MetaMorph software. (J) Methacycline prevented Purkinjie cell loss. (K) Methacycline decreased astrocyte activation (GFAP) and increased neuronal cell staining (NeuN). Quantified with MetaMorph software (SI Appendix, Fig. S8 B–D). All data were analyzed with GraphPad Prism. Differences between means were assessed by one-way ANOVA followed by post hoc tests. ****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05. The mean is displayed, and all error bars represent SE. We analyzed 10 mock, 7 mock and methacycline, 11 Zika, and 11 Zika and methacycline animals.