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Göttig, L.* ; Weiß, C.* ; Stubbe, M.* ; Hanrieder, L.* ; Hofmann, S.* ; Grodziecki, A.* ; Stadler, D.* ; Carpentier, A.* ; Protzer, U. ; Schreiner, S.

Apobec3A deamination functions are involved in antagonizing efficient human adenovirus replication and gene expression.

mBio 14:e0347822 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
Apobec3A is involved in the antiviral host defense, targeting nuclear DNA, introducing point mutations, and thereby activating DNA damage response (DDR). Here, we found a significant upregulation of Apobec3A during HAdV infection, including Apobec3A protein stabilization mediated by the viral proteins E1B-55K and E4orf6, which subsequently limited HAdV replication and most likely involved a deaminase-dependent mechanism. The transient silencing of Apobec3A enhanced adenoviral replication. HAdV triggered Apobec3A dimer formation and enhanced activity to repress the virus. Apobec3A decreased E2A SUMOylation and interfered with viral replication centers. A comparative sequence analysis revealed that HAdV types A, C, and F may have evolved a strategy to escape Apobec3A-mediated deamination via reduced frequencies of TC dinucleotides within the viral genome. Although viral components induce major changes within infected cells to support lytic life cycles, our findings demonstrate that host Apobec3A-mediated restriction limits virus replication, albeit that HAdV may have evolved to escape this restriction. This allows for novel insights into the HAdV/host-cell interplay, which broaden the current view of how a host cell can limit HAdV infection. IMPORTANCE Our data provide a novel conceptual insight into the virus/host-cell interplay, changing the current view of how a host-cell can defeat a virus infection. Thus, our study reveals a novel and general impact of cellular Apobec3A on the intervention of human adenovirus (HAdV) gene expression and replication by improving the host antiviral defense mechanisms, thereby providing a novel basis for innovative antiviral strategies in future therapeutic settings. Ongoing investigations of the cellular pathways that are modulated by HAdV are of great interest, particularly since adenovirus-based vectors actually serve as COVID vaccine vectors and also frequently serve as tools in human gene therapy and oncolytic treatment options. HAdV constitute an ideal model system by which to analyze the transforming capabilities of DNA tumor viruses as well as the underlying molecular principles of virus-induced and cellular tumorigenesis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter A3a ; Apobec ; Hadv ; Sumo ; Sumoylation ; Adenovirus ; Deamination ; Virus Host Interaction; Human-immunodeficiency-virus; Dependent Degradation; Monoclonal-antibodies; Cytidine Deaminase; Restriction Factor; Sumo Modification; Protein; Isoform; Binding; Transformation
ISSN (print) / ISBN 2150-7511
e-ISSN 2150-7511
Zeitschrift mBio
Quellenangaben Band: 14, Heft: 3, Seiten: , Artikelnummer: e0347822 Supplement: ,
Verlag American Society for Microbiology (ASM)
Verlagsort 1752 N St Nw, Washington, Dc 20036-2904 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Förderungen Deutsche Krebshilfe e.V.
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)