人巨细胞病毒AD169新型病毒白细胞介素-10亚型的鉴定
Identification of novel viral interleukin-10 isoforms of human cytomegalovirus AD169.
作者信息
Lin Yi-Ling, Chang Pei-Ching, Wang Yixiang, Li Mengtao
机构信息
Department of Oral Pathology, University of Kentucky College of Dentistry, 800 Rose Street, Lexington, KY 40536, USA.
出版信息
Virus Res. 2008 Feb;131(2):213-23. doi: 10.1016/j.virusres.2007.09.011. Epub 2007 Nov 5.
Abstract
Two products of human cytomegalovirus (HCMV) UL111a gene have been previously identified to resemble human IL-10 (hIL-10). These viral IL-10s (vIL-10s) are able to induce signal transduction events and biological activities in a variety of cells. In this study, five novel vIL-10 transcripts were identified from HCMV AD169 infected MRC-5 cells. Some vIL-10 isoforms were post-translationally glycosylated, depending on the existence of a predicted N-linked glycosylation site. Similar to hIL-10, four of the vIL-10 isoforms apparently formed putative dimers. Among the different vIL-10 isoforms, vIL-10A significantly induced the phosphorylation of transcription factor STAT3 in THP-1 cells. All identified vIL-10 isoforms were able to form complexes with hIL-10, and enhanced hIL-10-induced STAT3 phosphorylation in different degrees. Identification of diverse forms of vIL-10 suggests that HCMV has developed a sophisticated mechanism to interfere with hIL-10 signaling pathway.
摘要
先前已鉴定出人类巨细胞病毒（HCMV）UL111a基因的两种产物类似于人类白细胞介素10（hIL-10）。这些病毒白细胞介素10（vIL-10）能够在多种细胞中诱导信号转导事件和生物学活性。在本研究中，从HCMV AD169感染的MRC-5细胞中鉴定出了五种新的vIL-10转录本。一些vIL-10异构体在翻译后进行了糖基化，这取决于预测的N-连接糖基化位点的存在。与hIL-10相似，四种vIL-10异构体明显形成了假定的二聚体。在不同的vIL-10异构体中，vIL-10A显著诱导了THP-1细胞中转录因子STAT3的磷酸化。所有鉴定出的vIL-10异构体都能够与hIL-10形成复合物，并不同程度地增强hIL-10诱导的STAT3磷酸化。多种形式的vIL-10的鉴定表明，HCMV已经发展出一种复杂的机制来干扰hIL-10信号通路。
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