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麻疹病毒对宿主防御的逃避:野生型麻疹病毒感染会干扰α/β干扰素的产生诱导。

Evasion of host defenses by measles virus: wild-type measles virus infection interferes with induction of Alpha/Beta interferon production.

作者信息

Naniche D, Yeh A, Eto D, Manchester M, Friedman R M, Oldstone M B

机构信息

Division of Virology, Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.

出版信息

J Virol. 2000 Aug;74(16):7478-84. doi: 10.1128/jvi.74.16.7478-7484.2000.

Abstract

Measles is a highly contagious disease currently responsible for over one million childhood deaths, particularly in the developing world. Since alpha/beta interferons (IFNs) are pivotal players both in nonspecific antiviral immunity and in specific cellular responses, their induction or suppression by measles virus (MV) could influence the outcome of a viral infection. In this study we compare the IFN induction and sensitivity of laboratory-passaged attenuated MV strains Edmonston and Moraten with those of recent wild-type viruses isolated and passaged solely on human peripheral blood mononuclear cells (PBMC) or on the B958 marmoset B-cell line. We report that two PBMC-grown wild-type measles isolates and two B958-grown strains of MV induce 10- to 80-fold-lower production of IFN by phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) compared to Edmonston and Moraten strains of measles. Preinfection of PBL with these non-IFN-inducing MV isolates prevents Edmonston-induced but not double-stranded-RNA-induced IFN production. This suggests that the wild-type viruses can actively inhibit Edmonston-induced IFN synthesis and that this is not occurring by double-stranded RNA. Furthermore, the wild-type MV is more sensitive than Edmonston MV to the effect of IFN. MV is thus able to suppress the synthesis of the earliest mediator of antiviral immunity, IFN-alpha/beta. This could have important implications in the virulence and spread of MV.

摘要

麻疹是一种高度传染性疾病,目前导致超过100万儿童死亡,在发展中国家尤为严重。由于α/β干扰素(IFN)在非特异性抗病毒免疫和特异性细胞反应中均起关键作用,麻疹病毒(MV)对其的诱导或抑制可能会影响病毒感染的结果。在本研究中,我们比较了实验室传代的减毒MV毒株埃德蒙斯顿株和莫拉坦株与近期仅在人外周血单核细胞(PBMC)或B958狨猴B细胞系中分离和传代的野生型病毒的IFN诱导能力和敏感性。我们报告,与麻疹的埃德蒙斯顿株和莫拉坦株相比,两种在PBMC中培养的野生型麻疹分离株和两种在B958中培养的MV毒株,经植物血凝素刺激的外周血淋巴细胞(PBL)产生的IFN降低了10至80倍。用这些不诱导IFN的MV分离株对PBL进行预感染可阻止埃德蒙斯顿株诱导的IFN产生,但不能阻止双链RNA诱导的IFN产生。这表明野生型病毒可主动抑制埃德蒙斯顿株诱导的IFN合成,且这并非通过双链RNA发生。此外,野生型MV比埃德蒙斯顿MV对IFN的作用更敏感。因此,MV能够抑制抗病毒免疫的最早介质IFN-α/β的合成。这可能对MV 的毒力和传播具有重要意义。

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