Importance of the anti-interferon capacity of Sendai virus C protein for pathogenicity in mice
Importance of the anti-interferon capacity of Sendai virus C protein for pathogenicity in mice
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DOI：
10.1128/jvi.02590-06
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发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Nagai, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Kato, Atsushi;Kiyotani, Katsuhiro;Nagai, Yoshiyuki
仙台病毒（SeV） C蛋白阻断干扰素（IFN）的信号转导，从而抵消IFN的抗病毒作用。使用表达截断或突变的SeV C蛋白的HeLa细胞系，我们发现C端一半具有抗ifn的能力，并且C蛋白中的K(151)A， E(153)A和R(154)A取代消除了这种能力。在不改变重叠的P、V、W蛋白氨基酸序列的情况下，在C蛋白中引入K(151)A、(EK)-K-153和(RL)-L-157取代，进一步构建了突变病毒SeV Cm*。正如预期的那样，SeV Cm*缺乏抗ifn能力。虽然在ifn应答、stat1阳性的2fTGH细胞中，SeV Cm*的生长速度和最终产量低于野生型SeV，但在ifn不应答、stat1缺失的U3A细胞中，SeV Cm*的生长速度和最终产量与野生型SeV相当。因此，SeV Cm*除了缺乏抗ifn能力外，还保持了增殖能力。经鼻内接种的SeV Cm*可以在STAT1（-/-）小鼠的肺中繁殖，但在STAT1（+/+）小鼠的肺中被清除，无法繁殖。研究发现，SeV C蛋白的抗ifn能力是小鼠致病性不可缺少的。相反，结果表明先天免疫有助于在感染早期缺乏抗ifn能力的情况下消除SeV。
The Sendai virus (SeV) C protein blocks signal transduction of interferon (IFN), thereby counteracting the antiviral actions of IFN. Using HeLa cell lines expressing truncated or mutated SeV C proteins, we found that the C-terminal half has anti-IFN capacity, and that K(151)A, E(153)A, and R(154)A substitutions in the C protein eliminated this capacity. Here, we further created the mutant virus SeV Cm*, in which K(151)A, (EK)-K-153, and (RL)-L-157 substitutions in the C protein were introduced without changing the amino acid sequence of overlapped P, V, and W proteins. SeV Cm* was found to lack anti-IFN capacity, as expected. While the growth rate and final yield of SeV Cm* were inferior to those of the wild-type SeV in IFN-responsive, STAT1-positive 2fTGH cells, SeV Cm* grew equivalently to the wild-type SeV in IFN-nonresponsive, STAT1-deficient U3A cells. SeV Cm* was thus shown to maintain multiplication capacity, except that it lacked anti-IFN capacity. Intranasally inoculated SeV Cm* could propagate in the lungs of STAT1(-/-) mice but was cleared from those of STAT1(+/+) mice without propagation. It was found that the anti-IFN capacity of the SeV C protein was indispensable for pathogenicity in mice. Conversely, the results show that the innate immunity contributed to elimination of SeV in early stages of infection in the absence of anti-IFN capacity.