The SCHOOL of nature: IV. Learning from viruses.
The SCHOOL of nature: IV. Learning from viruses.
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DOI：
10.4161/self.1.4.13279
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发表时间：
2010-10-01
期刊：
影响因子：
--
通讯作者：
Sigalov, Alexander B
中科院分区：
文献类型：
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作者：
Sigalov, Alexander B
在病毒和宿主的共同进化过程中，宿主为自己配备了一套复杂的免疫系统，以防御入侵的病毒。为了建立成功的感染，在宿主中复制和持续存在，病毒进化出了许多策略来对抗和逃避宿主的抗病毒免疫反应，并利用它们进行有效的病毒复制。这些策略包括那些通过细胞表面受体调节信号的策略。尽管近年来取得了巨大的进展，但病毒致病机制中这些关键点的确切分子机制仍不清楚。在这项工作中，我基于一个新的受体信号转导平台--信号链HOMOL异构化平台，提出了不同病毒如人类免疫缺陷病毒(HIV)、巨细胞病毒(CMV)、严重急性呼吸综合征冠状病毒、人类疱疹病毒6等调节受体信号转导的具体机制。我还用HIV和CMV的例子来说明两种不相关的包膜病毒如何使用相似的学派机制来调节由两个功能不同的受体介导的宿主免疫反应：T细胞抗原受体和自然杀伤细胞受体NKp30。这表明，类似的一般机制很可能被其他病毒病原体或可能非病毒病原体使用。从病毒中学习如何靶向细胞表面受体不仅有助于我们了解病毒逃避宿主免疫监视的策略，而且为合理的药物设计和免疫疾病新疗法的开发提供了新的途径。
During the co-evolution of viruses and their hosts, the latter have equipped themselves with an elaborate immune system to defend themselves from the invading viruses. In order to establish a successful infection, replicate and persist in the host, viruses have evolved numerous strategies to counter and evade host antiviral immune responses as well as exploit them for productive viral replication. These strategies include those that modulate signaling mediated by cell surface receptors. Despite tremendous advancement in recent years, the exact molecular mechanisms underlying these critical points in viral pathogenesis remain unknown. In this work, based on a novel platform of receptor signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) platform, I suggest specific mechanisms used by different viruses such as human immunodeficiency virus (HIV), cytomegalovirus (CMV), severe acute respiratory syndrome coronavirus, human herpesvirus 6 and others, to modulate receptor signaling. I also use the example of HIV and CMV to illustrate how two unrelated enveloped viruses use a similar SCHOOL mechanism to modulate the host immune response mediated by two functionally different receptors: T cell antigen receptor and natural killer cell receptor, NKp30. This suggests that it is very likely that similar general mechanisms can be or are used by other viral and possibly non-viral pathogens. Learning from viruses how to target cell surface receptors not only helps us understand viral strategies to escape from the host immune surveillance, but also provides novel avenues in rational drug design and the development of new therapies for immune disorders.