title: Host restriction of murine gammaherpesvirus 68 replication by human APOBEC3 cytidine deaminases but not murine APOBEC3.
abstract: Humans encode seven APOBEC3 (A3A-A3H) cytidine deaminase proteins that differ in their expression profiles, preferred nucleotide recognition sequence and capacity for restriction of RNA and DNA viruses. We identified APOBEC3 hotspots in numerous herpesvirus genomes. To determine the impact of host APOBEC3 on herpesvirus biology in vivo, we examined whether murine APOBEC3 (mA3) restricts murine gammaherpesvirus 68 (MHV68). Viral replication was impaired by several human APOBEC3 proteins, but not mA3, upon transfection of the viral genome. The restriction was abrogated upon mutation of the A3A and A3B active sites. Interestingly, virus restriction by A3A, A3B, A3C, and A3DE was lost if the infectious DNA was delivered by the virion. MHV68 pathogenesis, including lung replication and splenic latency, was not altered in mice lacking mA3. We infer that mA3 does not restrict wild type MHV68 and restriction by human A3s may be limited in the herpesvirus replication process.
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Nana
authors.initials: N
authors.lastname: Minkah
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Chavez
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Parth
authors.initials: P
authors.lastname: Shah
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Maccarthy
authors.affiliation: Department of Microbiology, NYU Langone Medical Center, New York, NY 10016, USA; Infectious Disease Laboratory, Salk Institute, La Jolla, CA 92037, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Microbiology, NYU Langone Medical Center, New York, NY 10016, USA; Infectious Disease Laboratory, Salk Institute, La Jolla, CA 92037, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Landau
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: laurie.krug@stonybrook.edu.
authors.forename: Laurie T
authors.initials: LT
authors.lastname: Krug
mesh_terms: D000071478:APOBEC Deaminases; D000818:Animals; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018144:Rhadinovirus / Q000276:immunology* / Q000502:physiology*; D056189:Viral Tropism
chemical_list: D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase
keywords: APOBEC3; Cytidine deaminase; Herpesvirus; Host restriction; Latency; Murine gammaherpesvirus; Pathogenesis; Replication
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