生物
核糖核酸酶P
病毒
病毒学
干扰素
先天免疫系统
分子生物学
微小病毒
抗病毒蛋白
病毒复制
核糖核酸
免疫系统
生物化学
免疫学
基因
作者
Frédéric Sorgeloos,Babal K. Jha,Robert H. Silverman,Thomas Michiels
出处
期刊:PLOS Pathogens
[Public Library of Science]
日期:2013-06-27
卷期号:9 (6): e1003474-e1003474
被引量:63
标识
DOI:10.1371/journal.ppat.1003474
摘要
Theiler's virus is a neurotropic picornavirus responsible for chronic infections of the central nervous system. The establishment of a persistent infection and the subsequent demyelinating disease triggered by the virus depend on the expression of L*, a viral accessory protein encoded by an alternative open reading frame of the virus. We discovered that L* potently inhibits the interferon-inducible OAS/RNase L pathway. The antagonism of RNase L by L* was particularly prominent in macrophages where baseline oligoadenylate synthetase (OAS) and RNase L expression levels are elevated, but was detectable in fibroblasts after IFN pretreatment. L* mutations significantly affected Theiler's virus replication in primary macrophages derived from wild-type but not from RNase L-deficient mice. L* counteracted the OAS/RNase L pathway through direct interaction with the ankyrin domain of RNase L, resulting in the inhibition of this enzyme. Interestingly, RNase L inhibition was species-specific as Theiler's virus L* protein blocked murine RNase L but not human RNase L or RNase L of other mammals or birds. Direct RNase L inhibition by L* and species specificity were confirmed in an in vitro assay performed with purified proteins. These results demonstrate a novel viral mechanism to elude the antiviral OAS/RNase L pathway. By targeting the effector enzyme of this antiviral pathway, L* potently inhibits RNase L, underscoring the importance of this enzyme in innate immunity against Theiler's virus.
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