The APOBEC3B cytidine deaminase is an adenovirus restriction factor.

Autor: Lejeune N; Namur Research Institute for Life Sciences (NARILIS), Integrated Veterinary Research Unit (URVI), University of Namur, Namur, Belgium., Mathieu S; Namur Research Institute for Life Sciences (NARILIS), Integrated Veterinary Research Unit (URVI), University of Namur, Namur, Belgium., Decloux A; Namur Research Institute for Life Sciences (NARILIS), Integrated Veterinary Research Unit (URVI), University of Namur, Namur, Belgium., Poulain F; Namur Research Institute for Life Sciences (NARILIS), Integrated Veterinary Research Unit (URVI), University of Namur, Namur, Belgium., Blockx Z; Namur Research Institute for Life Sciences (NARILIS), Integrated Veterinary Research Unit (URVI), University of Namur, Namur, Belgium., Raymond KA; Département de Virologie, Institut Pasteur, Paris, France.; Sorbonne Université, Collège Doctoral, Paris, France., Willemart K; Namur Research Institute for Life Sciences (NARILIS), Integrated Veterinary Research Unit (URVI), University of Namur, Namur, Belgium., Vartanian JP; Département de Virologie, Institut Pasteur, Paris, France., Suspène R; Département de Virologie, Institut Pasteur, Paris, France., Gillet NA; Namur Research Institute for Life Sciences (NARILIS), Integrated Veterinary Research Unit (URVI), University of Namur, Namur, Belgium.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2023 Feb 06; Vol. 19 (2), pp. e1011156. Date of Electronic Publication: 2023 Feb 06 (Print Publication: 2023).
DOI: 10.1371/journal.ppat.1011156
Abstrakt: Human adenoviruses (HAdVs) are a large family of DNA viruses counting more than a hundred strains divided into seven species (A to G). HAdVs induce respiratory tract infections, gastroenteritis and conjunctivitis. APOBEC3B is a cytidine deaminase that restricts several DNA viruses. APOBEC3B is also implicated in numerous cancers where it is responsible for the introduction of clustered mutations into the cellular genome. In this study, we demonstrate that APOBEC3B is an adenovirus restriction factor acting through a deaminase-dependent mechanism. APOBEC3B introduces C-to-T clustered mutations into the adenovirus genome. APOBEC3B reduces the propagation of adenoviruses by limiting viral genome replication, progression to late phase, and production of infectious virions. APOBEC3B restriction efficiency varies between adenoviral strains, the A12 strain being more sensitive to APOBEC3B than the B3 or C2 strains. In A12-infected cells, APOBEC3B clusters in the viral replication centers. Importantly, we show that adenovirus infection leads to a reduction of the quantity and/or enzymatic activity of the APOBEC3B protein depending on the strains. The A12 strain seems less able to resist APOBEC3B than the B3 or C2 strains, a characteristic which could explain the strong depletion of the APOBEC3-targeted motifs in the A12 genome. These findings suggest that adenoviruses evolved different mechanisms to antagonize APOBEC3B. Elucidating these mechanisms could benefit the design of cancer treatments. This study also identifies adenoviruses as triggers of the APOBEC3B-mediated innate response. The involvement of certain adenoviral strains in the genesis of the APOBEC3 mutational signature observed in tumors deserves further study.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Lejeune et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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