Orzalli Megan H, Knipe David M
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115; email:
Annu Rev Microbiol. 2014;68:477-92. doi: 10.1146/annurev-micro-091313-103409. Epub 2014 Jun 16.
Mammalian cells detect foreign DNA introduced as free DNA or as a result of microbial infection, leading to the induction of innate immune responses that block microbial replication and the activation of mechanisms that epigenetically silence the genes encoded by the foreign DNA. A number of DNA sensors localized to a variety of sites within the cell have been identified, and this review focuses on the mechanisms that detect viral DNA and how the resulting responses affect viral infections. Viruses have evolved mechanisms that inhibit these host sensors and signaling pathways, and the study of these antagonistic viral strategies has provided insight into the mechanisms of these host responses. The field of cellular sensing of foreign DNA is in its infancy, but our currently limited knowledge has raised a number of important questions for study.
哺乳动物细胞能够检测到以游离DNA形式引入的或由于微生物感染而产生的外源DNA,从而引发先天免疫反应,阻止微生物复制,并激活从表观遗传学上使外源DNA编码的基因沉默的机制。已经鉴定出许多定位于细胞内各种位点的DNA传感器,本综述重点关注检测病毒DNA的机制以及由此产生的反应如何影响病毒感染。病毒已经进化出抑制这些宿主传感器和信号通路的机制,对这些拮抗病毒策略的研究为了解这些宿主反应的机制提供了线索。对外源DNA的细胞传感领域尚处于起步阶段,但我们目前有限的知识已经提出了许多重要的研究问题。