Role of core protein mutations in the development of occult HBV infection

•Amino acid (aa) substitutions in the core protein (Cp) of occult HBV infection (OBI) strains were identified.•An OBI mutant strain (SZA) carrying 9 aa substitutions in Cp was characterised in vitro (cells) and in vivo (mice).•The functional impact of individual aa substitutions in pHBV1.3-SZA Cp replicons was assessed in vitro and in vivo.•The Cp W62R mutation significantly reduced HBV protein production.•The Cp W62R and its combination mutations might contribute to the occurrence of OBI.