Grass carp SERPINA1 inhibits GCRV infection through degrading CF2.

Grass carp SERPINA1 inhibits GCRV infection through degrading CF2.
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DOI:
10.3389/fimmu.2022.969517
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发表时间:
2022
影响因子:
7.3
通讯作者:
Wang, Yaping
Wang, Yaping
中科院分区:
医学2区
文献类型:
--
作者:
Li, Yangyang;Chen, Liangming;Huang, Rong;Li, Yangyu;Yang, Cheng;Gui, Bin;Li, Yongming;Liao, Lanjie;Zhu, Zuoyan;Wang, Yaping

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SERPINA1 是丝氨酸蛋白酶抑制剂家族的成员,通过调节丝氨酸和半胱氨酸蛋白酶的活性在病毒感染和炎症中发挥作用。迄今为止,尚未见有关SERPINA1在鱼类免疫功能方面的报道。在本研究中,我们首先克隆了草鱼(Ctenopharyngodon idellus)的serpina1基因,发现其能够对草鱼呼肠孤病毒(GCRV)的感染做出快速反应,并且serpina1的过表达可以增强CIK细胞的抗病毒反应。制备SERPINA1多克隆抗体,并通过CoIP/MS在草鱼肝胰腺组织中筛选与SERPINA1相互作用的蛋白。研究发现,SERPINA1 与凝血因子 2 (CF2) 相互作用,并能以剂量依赖性方式降解它。此外,cf2的过表达有助于CIK细胞中GCRV的感染,而草鱼中serpina1和cf2的共表达减少了细胞中GCRV的拷贝数。结果表明,草鱼SERPINA1可以通过降解CF2来抑制GCRV感染。该研究提出SERPINA1可以通过与凝血因子的相互作用抑制病毒感染,为SERPINA1抗病毒功能的分子机制提供了新的见解。
SERPINA1, a member of the serine protease inhibitor family, plays a role in viral infection and inflammation by regulating the activities of serine and cysteine proteases. To date, there have been no reports on the immune function of SERPINA1 in fishes. In this study, we first cloned the serpina1 gene of grass carp (Ctenopharyngodon idellus) and found that it could respond rapidly to the infection of Grass carp reovirus (GCRV), and overexpression of serpina1 could enhance the antiviral response of CIK cells. A polyclonal antibody of SERPINA1 was prepared, and the protein interacting with SERPINA1 was screened by CoIP/MS in grass carp hepatopancreas tissue. It was found that SERPINA1 interacted with coagulation factor 2 (CF2) and could degrade it in a dose-dependent manner. In addition, overexpression of cf2 contributed to the infection of GCRV in CIK cells, whereas co-expression of serpina1 and cf2 in grass carp reduced the copy number of GCRV in cells. The results showed that grass carp SERPINA1 could inhibit GCRV infection by degrading CF2. This study proposes that SERPINA1 can inhibit viral infection through interaction with the coagulation factor, providing new insights into the molecular mechanism of SERPINA1’s antiviral function.
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