a. ΔMxra8 or control 3T3 or MEF cells were inoculated with CHIKV and stained for E2 protein (3 experiments, n = 9; two-tailed t-test with Holm-Sidak correction, ***, P < 0.001; ****, P < 0.0001; mean ± standard deviations (SD). b–d. Multi-step growth curves with CHIKV-181/25 (b), CHIKV-AF15561 (c), or CHIKV-LR-2006 (d) in control, ΔMxra8, or Mxra8 trans-complemented 3T3 cells (3 experiments, n = 9; mean ± SD). e. ΔMxra8 or control 3T3 cells were inoculated with alphaviruses and processed for E2 or reporter gene expression (3 or more experiments, n = 6 except for SFV, WEEV, and EEEV where n = 18; two-tailed t-test with Holm-Sidak correction, *, P < 0.05; ****, P < 0.0001; mean ± SD). f. ΔMxra8 or control 3T3 cells were inoculated with indicated viruses and processed for viral antigen or reporter gene expression (3 experiments, mean ± SD). g. HeLa cells were transduced with control or MXRA8-1, -2, -3, or -4 alleles, inoculated with CHIKV, and processed for E2 staining (3 experiments, n = 6; one-way ANOVA with Dunnett’s test, *, P < 0.05; **, P < 0.01; ***, P < 0.001; mean ± SD). h. Human MRC-5 cells depleted of MXRA8 with two different sgRNA were inoculated with CHIKV, and E2 expression was analyzed (3 experiments, n = 9; one-way ANOVA with Dunnett’s test, ****, P < 0.0001; mean ± SD).