title: Genetic editing of herpes simplex virus 1 and Epstein-Barr herpesvirus genomes by human APOBEC3 cytidine deaminases in culture and in vivo.
abstract: Human APOBEC3 cytidine deaminases target and edit single-stranded DNA, which can be of viral, mitochondrial, or nuclear origin. Retrovirus genomes, such as human immunodeficiency virus (HIV) genomes deficient in the vif gene and the hepatitis B virus genome, are particularly vulnerable. The genomes of some DNA viruses, such as human papillomaviruses, can be edited in vivo and in transfection experiments. Accordingly, herpesviruses should be no exception. This is indeed the case for herpes simplex virus 1 (HSV-1) in tissue culture, where APOBEC3C (A3C) overexpression can reduce virus titers and the particle/PFU ratio ∼10-fold. Nonetheless, A3A, A3G, and AICDA can edit what is presumably a small fraction of HSV genomes in an experimental setting without seriously impacting the viral titer. Hyperediting was found in HSV genomes recovered from 4/8 uncultured buccal lesions. The phenomenon is not restricted to HSV, since hyperedited Epstein-Barr virus (EBV) genomes were readily recovered from 4/5 established cell lines, indicating that episomes are vulnerable to editing. These findings suggest that the widely expressed A3C cytidine deaminase can function as a restriction factor for some human herpesviruses. That the A3C gene is not induced by type I interferons begs the question whether some herpesviruses encode A3C antagonists.
authors.affiliation: Molecular Retrovirology Unit, Institut Pasteur, CNRS URA 3015, 28 Rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Suspène
authors.forename: Marie-Ming
authors.initials: MM
authors.lastname: Aynaud
authors.forename: Stefanie
authors.initials: S
authors.lastname: Koch
authors.forename: David
authors.initials: D
authors.lastname: Pasdeloup
authors.forename: Marc
authors.initials: M
authors.lastname: Labetoulle
authors.forename: Barbara
authors.initials: B
authors.lastname: Gaertner
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vartanian
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyerhans
authors.forename: Simon
authors.initials: S
authors.lastname: Wain-Hobson
mesh_terms: D000071478:APOBEC Deaminases; D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D016679:Genome, Viral; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D004247:DNA; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase