Zhao-Yang Wang, Pei-Gang Wang and Jing An. The Multifaceted Roles of TAM Receptors during Viral Infection[J]. Virologica Sinica, 2021, 36(1): 1-12. doi: 10.1007/s12250-020-00264-9
Citation: Zhao-Yang Wang, Pei-Gang Wang, Jing An. The Multifaceted Roles of TAM Receptors during Viral Infection .VIROLOGICA SINICA, 2021, 36(1) : 1-12.  http://dx.doi.org/10.1007/s12250-020-00264-9

TAM受体在病毒感染过程中具有多方面的作用

  • 通讯作者: 王培刚, pgwang@ccmu.edu.cn, ORCID: http://orcid.org/0000-0001-6045-2007
    ; 安静, anjing@ccmu.edu.cn, ORCID: http://orcid.org/0000-0002-2946-7371
  • 收稿日期: 2020-04-18
    录用日期: 2020-06-08
    出版日期: 2020-07-27
  • Tyro3、Axl 和Mertk(TAM)受体在多种生理和病理过程中发挥着重要的作用,包括介导吞噬细胞对凋亡细胞和细胞碎片的清除、维持免疫和炎症稳态、维持血脑屏障完整性和中枢神经系统稳态,介导肿瘤恶性转化及化疗耐药等。生长阻滞特异性基因6(growth arrest-specific gene 6, Gas6)和蛋白质S(protein S, Pros1)是激活TAM受体的两种配体。最近报道,TAM 受体以“凋亡模拟”的方式介导多种包膜病毒的细胞进入和感染。TAM受体在病毒进入和感染期间被激活,并抑制天然免疫和炎症反应,促进病毒复制和免疫逃逸。然而在体内,这些病毒感染并不需要TAM受体。此外,TAM受体可保护小鼠中枢神经系统免受神经侵袭性病毒的感染,减轻脑炎时的脑病理损伤。这些保护作用是通过维持血脑屏障的完整性,减少炎性细胞因子的产生,以及促进神经细胞的存活而实现的。TAM受体还调节了病毒感染细胞的程序性死亡过程,从而影响病毒感染的发病过程。本文系统地综述了TAM受体在各种病毒感染过程中的多样性作用及其机制,并讨论了TAM受体拮抗剂在预防病毒性脑炎发病中的潜在应用。

The Multifaceted Roles of TAM Receptors during Viral Infection

  • Corresponding author: Pei-Gang Wang, pgwang@ccmu.edu.cn Jing An, anjing@ccmu.edu.cn
  • ORCID: http://orcid.org/0000-0001-6045-2007; http://orcid.org/0000-0002-2946-7371
  • Received Date: 18 April 2020
    Accepted Date: 08 June 2020
    Published Date: 27 July 2020
  • Tyro3, Axl, and Mertk (TAM) receptors play multiple roles in a myriad of physiological and pathological processes, varying from promoting the phagocytic clearance of apoptotic cells, sustaining the immune and inflammatory homeostasis, maintaining the blood-brain barrier (BBB) integrity and central nervous system (CNS) homeostasis, to mediating cancer malignancy and chemoresistance. Growth arrest-specific protein 6 (Gas6) and protein S (Pros1) are the two ligands that activate TAM receptors. Recently, TAM receptors have been reported to mediate cell entry and infection of multitudinous enveloped viruses in a manner called apoptotic mimicry. Moreover, TAM receptors are revitalized during viral entry and infection, which sequesters innate immune and inflammatory responses, facilitating viral replication and immune evasion. However, accumulating evidence have now proposed that TAM receptors are not required for the infection of these viruses in vivo. In addition, TAM receptors protect mice against the CNS infection of neuroinvasive viruses and relieve the brain lesions during encephalitis. These protective effects are achieved through maintaining BBB integrity, attenuating pro-inflammatory cytokine production, and promoting neural cell survival. TAM receptors also regulate the programmed cell death modes of virus-infected cells, which have profound impacts on the pathogenesis and outcome of infection. Here, we systematically review the functionalities and underlying mechanisms of TAM receptors and propose the potential application of TAM agonists to prevent severe viral encephalitis.


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    The Multifaceted Roles of TAM Receptors during Viral Infection

      Corresponding author: Pei-Gang Wang, pgwang@ccmu.edu.cn
      Corresponding author: Jing An, anjing@ccmu.edu.cn
    • 1. Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
    • 2. Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing 100093, China

    Abstract: 

    Tyro3, Axl, and Mertk (TAM) receptors play multiple roles in a myriad of physiological and pathological processes, varying from promoting the phagocytic clearance of apoptotic cells, sustaining the immune and inflammatory homeostasis, maintaining the blood-brain barrier (BBB) integrity and central nervous system (CNS) homeostasis, to mediating cancer malignancy and chemoresistance. Growth arrest-specific protein 6 (Gas6) and protein S (Pros1) are the two ligands that activate TAM receptors. Recently, TAM receptors have been reported to mediate cell entry and infection of multitudinous enveloped viruses in a manner called apoptotic mimicry. Moreover, TAM receptors are revitalized during viral entry and infection, which sequesters innate immune and inflammatory responses, facilitating viral replication and immune evasion. However, accumulating evidence have now proposed that TAM receptors are not required for the infection of these viruses in vivo. In addition, TAM receptors protect mice against the CNS infection of neuroinvasive viruses and relieve the brain lesions during encephalitis. These protective effects are achieved through maintaining BBB integrity, attenuating pro-inflammatory cytokine production, and promoting neural cell survival. TAM receptors also regulate the programmed cell death modes of virus-infected cells, which have profound impacts on the pathogenesis and outcome of infection. Here, we systematically review the functionalities and underlying mechanisms of TAM receptors and propose the potential application of TAM agonists to prevent severe viral encephalitis.