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首页> 外文期刊>Infection and immunity >The antichlamydial, antiviral, and antiproliferative activities of human gamma interferon are dependent on the integrity of the C terminus of the interferon molecule.
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The antichlamydial, antiviral, and antiproliferative activities of human gamma interferon are dependent on the integrity of the C terminus of the interferon molecule.

机译：人γ干扰素的抗衣原体，抗病毒和抗增殖活性取决于干扰素分子C末端的完整性。

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The effects of recombinant human gamma interferon (rHuIFN-gamma; two identical monomers of 140 residues in length) and of two re-engineered C-terminal variants, rHuIFN-gamma Tetra-Ser (residues 129 to 132 replaced by serine) and rHuIFN-gamma 125 (two identical monomers of 125 residues each with the last 14 residues plus an additional alanine from the C terminus deleted), were compared in terms of several in vitro biological activities. By using three different human cell lines (HeLa 229, HEp-2, and A549), the interferons were tested for their ability to inhibit: (i) growth of Chlamydia trachomatis; (ii) replication of encephalomyocarditis virus; and (iii) cell growth. rHuIFN-gamma restricted the growth of chlamydiae to 50% of the non-IFN-treated control at concentrations ranging from 0.01 to 0.05 ng/ml, depending on the cell type assayed. One of the modified proteins, rHuIFN-gamma Tetra-Ser, also decreased the growth of chlamydiae, but it required a concentration of approximately 0.5 ng/ml to produce 50% inhibition. rHuIFN-gamma 125 had the lowest antichlamydial activity of the three IFN-gamma variants tested; concentrations of 1 to 20 ng/ml were needed to reduce the growth of C. trachomatis to 50% of that of the control. The relative antiviral and antiproliferative activities of the three IFN-gamma preparations paralleled their antichlamydial activities in these three cell lines. The antiencephalomyocarditis virus activities of rHuIFN-gamma Tetra-Ser and rHuIFN-gamma 125 were reduced by approximately 10-fold and 10(2)- to 10(3)-fold, respectively, compared with the antiviral activity of rHuIFN-gamma. Proliferation of the three cell lines was restricted to approximately 50% of the control with 0.5 to 10 ng of rHuIFN-gamma per ml. Inhibition of cell growth by rHuIFN-gamma Tetra-Ser was significant only at concentrations equal to or greater than 30 ng/ml, and the rHuIFN-gamma 125 variant did not significantly decrease the growth of any of the three cell lines at the concentrations tested. These results suggest that the C-terminal portion of rHuIFN-gamma is critical for maintaining the conformation necessary for inducing the antichlamydial, antiviral, and antiproliferative activities of the molecule.
机译：重组人γ干扰素（rHuIFN-γ;两个相同的单体，长度为140个残基）和两个重新设计的C末端变体，rHuIFN-γTetra-Ser（残基129至132被丝氨酸取代）和rHuIFN-根据几种体外生物学活性比较了γ125（两个相同的125个残基的单体，每个残基具有最后的14个残基，另外一个丙氨酸已从C末端缺失）。通过使用三种不同的人类细胞系（HeLa 229，HEp-2和A549），测试了干扰素的抑制能力：（i）沙眼衣原体的生长; （ii）脑心肌炎病毒的复制; （iii）细胞生长。根据测定的细胞类型，rHuIFN-γ在0.01至0.05 ng / ml的浓度范围内将衣原体的生长限制在未经IFN处理的对照组的50％。修饰的蛋白质之一，rHuIFN-γTetra-Ser，也减少了衣原体的生长，但需要约0.5 ng / ml的浓度才能产生50％的抑制作用。在测试的三种IFN-γ变体中，rHuIFN-γ125的抗衣原体活性最低。需要浓度为1到20 ng / ml的浓度才能将沙眼衣原体的生长降低到对照组的50％。三种IFN-γ制剂的相对抗病毒和抗增殖活性与这三种细胞系的抗衣原体活性平行。与rHuIFN-γ的抗病毒活性相比，rHuIFN-γTetra-Ser和rHuIFN-γ125的抗脑心肌炎病毒活性分别降低了约10倍和10（2）-至10（3）倍。用每毫升0.5至10 ngrHuIFN-γ将这三种细胞系的增殖限制在对照的约50％。仅在等于或大于30 ng / ml的浓度下，rHuIFN-γTetra-Ser对细胞生长的抑制作用才显着，并且在所测试的浓度下，rHuIFN-γ125变体不会显着降低三种细胞系的生长。这些结果表明，rHuIFN-γ的C末端部分对于维持诱导该分子的抗衣原体，抗病毒和抗增殖活性所必需的构象至关重要。

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