The brain parenchyma has a type I interferon response that can limit virus spread

被引:41
作者
Drokhlyansky, Eugene [1 ,2 ,3 ]
Ayturka, Didem Goz [1 ,2 ,3 ]
Soh, Timothy K. [4 ]
Chrenek, Ryan [1 ,2 ,3 ]
O'Loughlin, Elaine [5 ]
Madore, Charlotte [5 ]
Butovsky, Oleg [5 ]
Cepko, Constance L. [1 ,2 ,3 ]
机构
[1] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA
[2] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA
[3] Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA
[4] Harvard Med Sch, Program Virol, Dept Microbiol & Immunobiol, Boston, MA 02115 USA
[5] Harvard Med Sch, Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
vesicular stomatitis virus; VSV; brain; innate immunity; interferon; VESICULAR STOMATITIS-VIRUS; CENTRAL-NERVOUS-SYSTEM; EPITHELIAL-CELLS; GENE-EXPRESSION; HOST FACTORS; INFECTION; IMAGE; RNA; PARTICLES; NEURONS;
D O I
10.1073/pnas.1618157114
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The brain has a tightly regulated environment that protects neurons and limits inflammation, designated "immune privilege." However, there is not an absolute lack of an immune response. We tested the ability of the brain to initiate an innate immune response to a virus, which was directly injected into the brain parenchyma, and to determine whether this response could limit viral spread. We injected vesicular stomatitis virus (VSV), a transsynaptic tracer, or naturally occurring VSV-derived defective interfering particles (DIPs), into the caudate-putamen (CP) and scored for an innate immune response and inhibition of virus spread. We found that the brain parenchyma has a functional type I interferon (IFN) response that can limit VSV spread at both the inoculation site and among synaptically connected neurons. Furthermore, we characterized the response of microglia to VSV infection and found that infected microglia produced type I IFN and uninfected microglia induced an innate immune response following virus injection.
引用
收藏
页码:E95 / E104
页数:10
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