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

Author:

Khalfi Pierre12,Suspène Rodolphe1,Caval Vincent1,Thiers Valérie1,Beauclair Guillaume3,Marchio Agnès4,Bekondi Claudine5,Amougou Atsama Marie6,Camengo-Police Serge Magloire7,Noah Noah Dominique8,Njouom Richard6,Blanc Hervé9,Vallet Thomas9,Vignuzzi Marco9ORCID,Pineau Pascal4,Vartanian Jean Pierre1

Affiliation:

1. Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR3569 , Paris , France

2. Commissariat à l’Énergie Atomique et aux Énergies Alternatives, Sorbonne Université , Paris , France

3. Institute for Integrative Biology of the Cell, Université Paris-Saclay, CEA, CNRS , Gif-sur-Yvette , France

4. Nuclear Organization and Oncogenesis unit, INSERM U993, Institut Pasteur, Université de Paris , Paris , France

5. Retrovirology and Oncogenic Viruses Unit, Institut Pasteur de Bangui , Bangui , Central African Republic

6. Virology Service, Centre Pasteur du Cameroun , Yaoundé , Cameroun

7. Gastroenterology Service, Hôpital Central , Yaoundé , Cameroun

8. Gastroenterology Service, Hôpital de l’Amitié , Bangui , Central African Republic

9. Viral Populations and Pathogenesis Unit, Institut Pasteur, Université de Paris, CNRS UMR3569 , Paris , France

Abstract

Abstract 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 APOBEC3CS188I. Using next-generation sequencing, we demonstrated that APOBEC3CS188I led to enhanced editing activity in 5ʹTpCpA→5ʹTpTpA context. This constitutes a new hallmark of this enzyme, which could be used to determine its impact on HBV or nuclear DNA.

Funder

Institut Pasteur

Institut Pasteur International Network

Ligue Contre le Cancer

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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