慢性病毒感染中 T 细胞反应的对跖点处的耗竭与扩张。

Exhaustion and Inflation at Antipodes of T Cell Responses to Chronic Virus Infection.

机构信息

Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany; Institute for Virology, Medical School Hannover, Hannover, Germany; German Center for Infection Research (DZIF), Partner site Hannover/Braunschweig, Germany.

Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Trends Microbiol. 2018 Jun;26(6):498-509. doi: 10.1016/j.tim.2017.11.012. Epub 2017 Dec 14.

Abstract

Viruses that have coevolved with their host establish chronic infections that are well tolerated by the host. Other viruses, that are partly adapted to their host, may induce chronic infections where persistent replication and viral antigen expression occur. The former induce highly functional and resilient CD8T cell responses called memory inflation. The latter induce dysfunctional and exhausted responses. The reasons compelling T cell responses towards inflationary or exhausted responses are only partly understood. In this review we compare the two conditions and describe mechanistic similarities and differences. We also provide a list of potential reasons why exhaustion or inflation occur in different virus infections. We propose that T cell-mediated transcriptional repression of viral gene expression provides a critical feature of inflation that allows peaceful virus and host coexistence. The virus is controlled, but its genome is not eradicated. If this mechanism is not available, as in the case of RNA viruses, the virus and the host are compelled to an arms race. If virus proliferation and spread proceed uncontrolled for too long, T cells are forced to strike a balance between viral control and tissue destruction, losing antiviral potency and facilitating virus persistence.

摘要

与宿主共同进化的病毒会建立慢性感染,而宿主通常能够很好地耐受这种感染。而那些部分适应宿主的病毒可能会引发慢性感染,导致持续复制和病毒抗原表达。前者会引发高度功能性和有弹性的 CD8T 细胞反应,称为记忆膨胀。后者则会引发功能失调和耗竭的反应。促使 T 细胞反应向膨胀或耗竭反应发展的原因目前仅部分被理解。在这篇综述中,我们比较了这两种情况,并描述了它们在机制上的相似和不同之处。我们还提供了一份可能导致不同病毒感染中出现耗竭或膨胀的潜在原因的清单。我们提出,T 细胞介导的病毒基因表达转录抑制为膨胀提供了一个关键特征,允许病毒与宿主和平共处。病毒受到控制,但它的基因组并未被根除。如果这种机制不存在,如在 RNA 病毒的情况下,病毒和宿主就会被迫进行军备竞赛。如果病毒的增殖和传播不受控制地持续太久,T 细胞就会被迫在病毒控制和组织破坏之间取得平衡,从而失去抗病毒效力并促进病毒持续存在。

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