Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox
Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox
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DOI：
10.1128/jvi.75.3.1205-1210.2001
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发表时间：
2001-02-01
影响因子：
5.4
通讯作者：
Ramshaw, IA
中科院分区：
文献类型：
--
作者：
Jackson, RJ;Ramsay, AJ;Ramshaw, IA
对临床鼠痘病毒的遗传抗性在近亲繁殖的实验室小鼠中有所不同，其特点是有效的自然杀伤（NK）反应和抗性小鼠早期强烈的CD8（+）细胞毒性t淋巴细胞（CTL）反应。我们研究了病毒表达的小鼠白细胞介素-4 （IL-4）在感染过程中对细胞介导反应的影响。结果表明，胸腺嘧啶激酶阳性的嗜电瘤病毒表达IL-4可抑制NK和CTL的细胞溶解反应以及后者对γ干扰素的表达。具有遗传抗性的小鼠感染了表达IL-4的病毒，出现了急性鼠痘的症状，并伴有高死亡率，类似于遗传敏感的小鼠感染了致命的莫斯科毒株时所见的疾病。引人注目的是，用表达IL-4的病毒感染最近免疫的遗传抗性小鼠也导致了暴发性鼠痘的显著死亡率。因此，这些数据表明，病毒编码的IL-4不仅可以抑制初级抗病毒细胞介导的免疫反应，还可以抑制免疫记忆反应的表达。
Genetic resistance to clinical mousepox (ectromelia virus) varies among inbred laboratory mice and is characterized by an effective natural killer (NK) response and the early onset of a strong CD8(+) cytotoxic T-lymphocyte (CTL) response in resistant mice. We have investigated the influence of virus expressed mouse interleukin-4 (IL-4) on the cell-mediated response during infection. It was observed that expression of IL-4 by a thymidine kinase-positive ectromelia virus suppressed cytolytic responses of NK and CTL and the expression of gamma interferon by the latter. Genetically resistant mice infected with the IL-4 expressing virus developed symptoms of acute mousepox accompanied by high mortality, similar to the disease seen when genetically sensitive mice are infected with the virulent Moscow strain. Strikingly, infection of recently immunized genetically resistant mice with the virus expressing IL-4 also resulted in significant mortality due to fulminant mousepox. These data therefore suggest that virus-encoded IL-4 not only suppresses primary antiviral cell-mediated immune responses but also can inhibit the expression of immune memory responses.