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白细胞介素-6缺陷小鼠中鼠γ-疱疹病毒68感染的发病机制

Pathogenesis of murine gammaherpesvirus-68 infection in interleukin-6-deficient mice.

作者信息

Sarawar S R, Brooks J W, Cardin R D, Mehrpooya M, Doherty P C

机构信息

St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, Tennessee, 38105, USA.

出版信息

Virology. 1998 Sep 30;249(2):359-66. doi: 10.1006/viro.1998.9309.

DOI:10.1006/viro.1998.9309
PMID:9791027
Abstract

Murine gammaherpesvirus-68 (MHV-68) induces high levels of interleukin (IL)-6 production in both naive and primed lymphocyte populations. Mice that are homozygous (-/-) for deletion of the IL-6 gene were used to investigate the role of this cytokine in MHV-68 infection. The results showed that IL-6 is not essential for clearance of infectious MHV-68 from the lung or for the establishment, or control, of viral latency. Both IL-6 +/+ and -/- mice eliminated replicating virus from the respiratory tract within 15 days of infection, and their lungs remained clear of infectious virus for >/=150 days. Interestingly, the IL-6 -/- mice had both increased numbers of natural killer (NK)1.1+ cells and higher levels of NK cell activity than the +/+ controls at 10-15 days after infection. However, there was no difference in the cytotoxic T cell activity between the two groups of mice. Levels of latent virus were comparable in IL-6 +/+ and -/- mice over the time course studied. Furthermore, analysis of the numbers, types, and activation status of the various leukocyte subsets (other than NK cells) in the bronchoalveolar lavage population, lymph nodes, and spleens of +/+ and -/- mice revealed no striking differences. Apart from the expected lack of IL-6, cytokine profiles were not dramatically altered in IL-6 -/- mice. Thus, there is no evidence for an obligatory role for IL-6 in T cell activation during infection with MHV-68.

摘要

小鼠γ疱疹病毒68型(MHV - 68)在未致敏和已致敏淋巴细胞群体中均可诱导高水平的白细胞介素(IL)-6产生。利用白细胞介素6基因缺失的纯合子(- / -)小鼠来研究这种细胞因子在MHV - 68感染中的作用。结果表明,IL - 6对于从肺部清除感染性MHV - 68或对于病毒潜伏的建立或控制并非必不可少。IL - 6 + / +和 - / -小鼠在感染后15天内均从呼吸道清除了复制病毒,并且它们的肺部在≥150天内均未检测到感染性病毒。有趣的是,在感染后10 - 15天,IL - 6 - / -小鼠的自然杀伤(NK)1.1 +细胞数量增加且NK细胞活性水平高于 + / +对照组。然而,两组小鼠的细胞毒性T细胞活性没有差异。在所研究的时间过程中,IL - 6 + / +和 - / -小鼠中的潜伏病毒水平相当。此外,对 + / +和 - / -小鼠的支气管肺泡灌洗群体、淋巴结和脾脏中各种白细胞亚群(NK细胞除外)的数量、类型和活化状态进行分析,未发现明显差异。除了预期的IL - 6缺乏外,IL - 6 - / -小鼠的细胞因子谱没有显著改变。因此,没有证据表明IL - 6在MHV - 68感染期间的T细胞活化中起必需作用。

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