APOBEC1-Mediated Editing and Attenuation of Herpes Simplex Virus 1 DNA Indicate That Neurons Have an Antiviral Role during Herpes Simplex Encephalitis
APOBEC1-Mediated Editing and Attenuation of Herpes Simplex Virus 1 DNA Indicate That Neurons Have an Antiviral Role during Herpes Simplex Encephalitis
复制标题
DOI：
10.1128/jvi.05288-11
复制
发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Koyanagi, Yoshio
中科院分区：
文献类型：
--
作者：
Gee, Peter;Ando, Yoshinori;Koyanagi, Yoshio
APOBEC 1（A1）是一种参与小肠脂质调节的胞苷脱氨酶。单纯疱疹病毒1（HSV-1）是一种普遍存在的病原体，能够感染大脑中的神经元，引起脑炎。在这里，我们表明，A1是诱导脑炎期间感染HSV-1的大鼠神经元。在稳定表达A1的细胞中，HSV-1感染导致病毒复制与对照细胞相比显著减少。如果A1表达被特异性A1短发夹RNA（shRNA）沉默，则可以将表达恢复到与对照细胞观察到的水平相当的水平。此外，胞苷脱氨酶活性似乎是这种抑制所必需的，并导致病毒mRNA转录物和DNA拷贝数的累积受损。从感染的表达A1的细胞中提取的病毒基因UL 54 DNA的测序显示了G到A和C到T的转换，表明A1与HSV-1 DNA相关。两者合计，我们的研究结果表明，在模型中，A1诱导脑炎期间的神经元可能有助于挫败HSV-1感染。
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.