BVDV: A pestivirus inducing tolerance of the innate immune response
BVDV: A pestivirus inducing tolerance of the innate immune response
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DOI：
10.1016/j.biologicals.2012.07.006
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发表时间：
2013-01-01
期刊：
影响因子：
1.7
通讯作者：
Schweizer, Matthias
中科院分区：
文献类型：
--
作者：
Peterhans, Ernst;Schweizer, Matthias
持续感染牛病毒性腹泻病毒（BVDV）的动物保持菌株特异性B和t细胞免疫耐受性。鼠疫病毒RNA触发干扰素（IFN）合成，病毒RNase E-rns抑制细胞外病毒RNA诱导的IFN表达。此外，N-pro促进转录因子IRF-3的降解，有效阻断bvdv感染细胞中IFN的表达。由于在PI动物中并非所有的潜在靶细胞都被感染，因此这些细胞与BVDV是“嵌合的”。这表明N-pro和E-rns是分别作用于感染和非感染细胞的非冗余IFN拮抗剂。此外，E-rns可能具有自相矛盾的功能，既是毒力因子，也是“衰减”因子：前者通过阻止先天免疫系统的激活，从而阻止适应性免疫系统的激活，后者通过最小化系统性IFN产生的有害影响。因此，BVDV通过避免IFN的诱导而保持“自我耐受性”，同时自身对IFN具有很大的抗性，但不会干扰IFN对无关病毒（“非自身”）的作用。这种独特的“自我”延伸到病毒上，表明宿主自身的RNA可能已经进化为一种防御宿主RNA无意中激活先天免疫系统的防御机制，从而建立了一种“先天耐受”状态。(C) 2012国际生物标准化联盟。Elsevier Ltd.出版。版权所有。
Animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) retain a strain-specific B- and T-cell immunotolerance. Pestiviral RNA triggers interferon (IFN) synthesis, and the viral RNase E-rns inhibits IFN expression induced by extracellular viral RNA. In addition, N-pro promotes the degradation of the transcription factor IRF-3, which effectively blocks IFN expression in BVDV-infected cells. As not all the potential target cells are infected in PI animals, these are 'chimeric' with respect to BVDV. This suggests that N-pro and E-rns are non-redundant IFN antagonists that act in infected and non-infected cells, respectively. Moreover, E-rns may take a paradoxical function, both as virulence as well as "attenuation" factor: The former by preventing the activation of the innate and, consequently, of the adaptive immune system, the latter by minimizing the detrimental effects of systemic IFN production. Thus, BVDV maintains "self-tolerance" by avoiding the induction of IFN while itself being largely resistant to it without, however, interfering with the IFN action against unrelated viruses ('nonself'). This unique extension of 'self' to a virus suggests that the host's own RNases may have evolved as a guard against inadvertent activation of the innate immune system by host RNA, thus establishing a state of "innate tolerance". (C) 2012 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.