title: The innate antiviral factor APOBEC3G targets replication of measles, mumps and respiratory syncytial viruses.
abstract: The cytidine deaminase APOBEC3G (apolipoprotein B mRNA-editing enzyme-catalytic polypeptide 3G; A3G) exerts antiviral activity against retroviruses, hepatitis B virus, adeno-associated virus and transposable elements. We assessed whether the negative-strand RNA viruses measles, mumps and respiratory syncytial might be affected by A3G, and found that their infectivity was reduced by 1-2 logs (90-99 %) in A3G overexpressing Vero cells, and in T-cell lines expressing A3G at physiological levels. Viral RNA was co-precipitated with HA-tagged A3G and could be amplified by RT-PCR. Interestingly, A3G reduced viral transcription and protein expression in infected cells by 50-70 %, and caused an increased mutation frequency of 0.95 mutations per 1000 nt in comparison to the background level of 0.22/1000. The observed mutations were not specific for A3G [cytidine to uridine (C→U) or guanine to adenine (G→A) hypermutations], nor specific for ADAR (adenosine deaminase acting on RNA, A→G and U→C transitions, with preference for next neighbour-nucleotides U = A>C>G). In addition, A3G mutants with inactivated catalytic deaminase (H257R and E259Q) were inhibitory, indicating that the deaminase activity is not required for the observed antiviral activity. In combination, impaired transcription and increased mutation frequencies are sufficient to cause the observed reduction in viral infectivity and eliminate virus replication within a few passages in A3G-expressing cells.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Fehrholz
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kendl
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Prifert
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Weissbrich
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Belfast, UK.
authors.forename: Ken
authors.initials: K
authors.lastname: Lemon
authors.affiliation: Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston University, Boston, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Rennick
authors.affiliation: Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston University, Boston, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Duprex
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Belfast, UK.
authors.forename: Bert K
authors.initials: BK
authors.lastname: Rima
authors.affiliation: Department of Infectious Diseases, King's College, London, UK.
authors.forename: Fransje A
authors.initials: FA
authors.lastname: Koning
authors.affiliation: Department of Infectious Diseases, King's College, London, UK.
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Holmes
authors.affiliation: Department of Infectious Diseases, King's College, London, UK.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Malim
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schneider-Schaulies
mesh_terms: D000071480:APOBEC-3G Deaminase; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D002460:Cell Line; D003564:Cytidine Deaminase / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008459:Measles virus / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D009109:Mumps virus / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D017354:Point Mutation; D012367:RNA, Viral / Q000235:genetics; D012136:Respiratory Syncytial Viruses / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase