DNMT3a can downregulate viral protein production. Huh7 cells were cotransfected with full-length HBV and empty vector, full-length HBV and methylated (inactivated) DNMT3a vectors, full-length HBV and DNMT3a vectors, and fully methylated HBV plus empty vector. All data are shown as means ± standard errors of means. Transfection with the methylated DNMT3a vectors did not affect the levels of HBsAg or HBeAg production (P = 0.14 and 0.57, respectively, by Student t tests). However, transfection with DNMT3a vectors significantly reduced both HBsAg and HBeAg secretion (P < 0.001 for both). As expected, methylation of HBV prior to transfection also significantly reduced both HBsAg and HBeAg secretion (P < 0.001 for both).