APOBEC1-mediated Editing and Attenuation of Herpes Simplex Virus 1 DNA Indicate That Neurons Have an Antiviral Role During Herpes Simplex Encephalitis

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2011 Jul 22

PMID 21775448

Citations 31

Authors

Peter Gee

Yoshinori Ando

Hiroko Kitayama

Seiji P Yamamoto

Yuka Kanemura

Hirotaka Ebina

Yasushi Kawaguchi

Yoshio Koyanagi

Affiliations

Soon will be listed here.

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.

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