ER stress-related proteins inositol demand protein 1α (IRE1α), activating transcription factor 6 (ATF6), PRKR-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2 (eIF2), X-Box binding protein 1 (XBP1), C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) were significantly upregulated in hepatitis B surface mutants. This evidence concerns the gene EIF2AK3 and hepatitis B virus infection.