APOBEC3C S188I Polymorphism Enhances Context-Specific Editing of Hepatitis B Virus Genome

In this study, we demonstrated in culture and in patients that HBV could be edited by APOBEC3C(S188I). This enzyme led to an enhanced editing activity in a more specific 5MODIFIER LETTER PRIMETpCpA -> 5MODIFIER LETTER PRIMETpTpA context. This constitutes a new hallmark of APOBEC3C(S188I). Single-nucleotide polymorphism in APOBEC3C (resulting in a serine to isoleucine in position 188) is present in approximately 10% of African populations and greatly enhances restriction against human immunodeficiency virus-1 and simian immunodeficiency virus by improving dimerization and DNA processivity of the enzyme. In this study, we demonstrated in culture and in infected patients that hepatitis B virus (HBV) could be edited by APOBEC3C(S188I). Using next-generation sequencing, we demonstrated that APOBEC3C(S188I) led to enhanced editing activity in 5MODIFIER LETTER PRIMETpCpA -> 5MODIFIER LETTER PRIMETpTpA context. This constitutes a new hallmark of this enzyme, which could be used to determine its impact on HBV or nuclear DNA.

Automated summary

This study demonstrates that APOBEC3C(S188I) editing enzyme can enhance the editing activity against HBV. Given the polymorphism of this editing enzyme in African populations and its restriction effect on immunodeficiency viruses, this finding holds significant implications.