Antivirus activity, but not thiolreductase activity, is conserved in interferon-gamma-inducible GILT protein in arthropod
Antivirus activity, but not thiolreductase activity, is conserved in interferon-gamma-inducible GILT protein in arthropod
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DOI：
10.1016/j.molimm.2021.10.018
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发表时间：
2021-11-10
影响因子：
3.6
通讯作者：
Kubo，Yoshinao
中科院分区：
文献类型：
--
作者：
Izumida，Mai;Hayashi，Hideki;Kubo，Yoshinao
我们以前曾报道，干扰素诱导的溶酶体硫醇还原酶(GILT)通过消化病毒被膜蛋白上的二硫键作为宿主防御因子来对抗逆转录病毒。金银被广泛保存，甚至在植物和真菌中也是如此。哺乳动物的硫醇还原酶活性部位由一个CXXC氨基酸基序组成，而在节肢动物中，包括虾、蟹和苍蝇在内的节肢动物的C端半胱氨酸残基被改变为丝氨酸。斑节对虾(Penaeus monodon，PmGILT)也含有CXXS基序而不是CXXC活性中心。我们在这里证明了一个带有CXXS基序和PmGILT基序的人GILT突变体(GILT C75S)在不改变其表达水平和溶酶体定位的情况下显著抑制两性小鼠白血病病毒载体在人细胞中的感染，表明活性部位的C末端半胱氨酸残基不是抗病毒活性所必需的。我们已经报道，人的镀金通过消化CD63上的二硫键来抑制HIV-1颗粒的产生。然而，GILT C75S突变体和PmGILT不能消化CD63二硫键，对HIV-1病毒粒子的产生也没有影响，表明它们不具有硫醇还原酶活性。综上所述，这项研究发现，抗病毒活性，而不是硫醇还原酶活性，在节肢动物金发蛋白中是保守的。这一发现提供了一个新的见解，即GILT在许多动物中的共同功能是抗病毒活性。
We have previously reported that gamma-interferon inducible lysosomal thiolreductase (GILT) functions as a host defense factor against retroviruses by digesting disulfide bonds on viral envelope proteins. GILT is widely conserved even in plants and fungi as well as animals. The thiolreductase active site of mammalian GILT is composed of a CXXC amino acid motif, whereas the C-terminal cysteine residue is changed to serine in arthropods including shrimps, crabs, and flies. GILT fromPenaeus monodon(PmGILT) also has the CXXS motif instead of the CXXC active site. We demonstrate here that a human GILT mutant (GILT C75S) with the CXXS motif and PmGILT significantly inhibit amphotropic murine leukemia virus vector infection in human cells without alterning its expression level and lysosomal localization, showing that the C-terminal cysteine residue of the active site is not required for the antiviral activity. We have reported that human GILT suppresses HIV-1 particle production by digestion of disulfide bonds on CD63. However, GILT C75S mutant and PmGILT did not digest CD63 disulfide bonds, and had no effect on HIV-1 virion production, suggesting that they do not have thiolreductase activity. Taken together, this study found that antiviral activity, but not thiolreductase activity, is conserved in arthropod GILT proteins. This finding provides a new insight that the common function of GILT is antiviral activity in many animals.