title: APOBEC1-mediated editing and attenuation of herpes simplex virus 1 DNA indicate that neurons have an antiviral role during herpes simplex encephalitis.
abstract: APOBEC1 (A1) is a cytidine deaminase involved in the regulation of lipids in the small intestine. Herpes simplex virus 1 (HSV-1) is a ubiquitous pathogen that is capable of infecting neurons in the brain, causing encephalitis. Here, we show that A1 is induced during encephalitis in neurons of rats infected with HSV-1. In cells stably expressing A1, HSV-1 infection resulted in significantly reduced virus replication compared to that in control cells. Infectivity could be restored to levels comparable to those observed for control cells if A1 expression was silenced by specific A1 short hairpin RNAs (shRNA). Moreover, cytidine deaminase activity appeared to be essential for this inhibition and led to an impaired accumulation of viral mRNA transcripts and DNA copy numbers. The sequencing of viral gene UL54 DNA, extracted from infected A1-expressing cells, revealed G-to-A and C-to-T transitions, indicating that A1 associates with HSV-1 DNA. Taken together, our results demonstrate a model in which A1 induction during encephalitis in neurons may aid in thwarting HSV-1 infection.
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Peter
authors.initials: P
authors.lastname: Gee
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ando
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kitayama
authors.forename: Seiji P
authors.initials: SP
authors.lastname: Yamamoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanemura
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ebina
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
mesh_terms: D000071479:APOBEC-1 Deaminase; D000818:Animals; D003564:Cytidine Deaminase / Q000276:immunology* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D004195:Disease Models, Animal; D020803:Encephalitis, Herpes Simplex / Q000276:immunology* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000254:growth & development* / Q000472:pathogenicity*; D009474:Neurons / Q000276:immunology / Q000821:virology; D012367:RNA, Viral / Q000378:metabolism; D051381:Rats; D012376:Rodent Diseases / Q000276:immunology / Q000821:virology; D016019:Survival Analysis; D014774:Virulence; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D004247:DNA; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605091:Apobec1 protein, rat; D003564:Cytidine Deaminase