Role of the myxoma virus soluble CC-chemokine inhibitor glycoprotein, M-T1, during myxoma virus pathogenesis
Role of the myxoma virus soluble CC-chemokine inhibitor glycoprotein, M-T1, during myxoma virus pathogenesis
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DOI：
10.1006/viro.1999.9617
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发表时间：
1999-04-10
期刊：
影响因子：
3.7
通讯作者：
McFadden, G
中科院分区：
文献类型：
--
作者：
Lalani, AS;Masters, J;McFadden, G
粘液瘤病毒是一种痘病毒，可在欧洲兔子中引起一种称为粘液瘤病的致命全身性疾病。与许多痘病毒一样，粘液瘤病毒编码多种分泌蛋白，可破坏宿主细胞因子的抗病毒活性。最近证明，粘液瘤病毒 M-T1 糖蛋白是痘病毒分泌蛋白大家族的成员，可结合 CC 趋化因子并在体外抑制其趋化活性。为了确定 M-T1 在粘液瘤病毒毒力中的生物学作用，我们构建了一种 M-T1 表达缺陷的重组 M-T1 缺失突变病毒。在这里，我们证明 M-T1 在粘液瘤病毒感染过程中作为高度稳定的 43-kDa 糖蛋白持续表达，并且对于病毒体外复制是必需的。 M-T1的缺失对受感染的欧洲兔子的疾病进展或总体死亡率没有显着影响，但在感染的最初2至3天期间加剧了原发组织部位的局部细胞炎症。在缺乏 M-T1 表达的情况下，病毒接种主要部位周围的深层真皮组织显示浸润白细胞，特别是单核细胞/巨噬细胞急剧增加，但这些吞噬细胞在清除病毒感染方面仍然相对无效，可能是由于其他分泌性粘液瘤病毒蛋白的协同特性。我们得出的结论是，M-T1 在体内粘液瘤病毒感染的急性期反应期间抑制单核细胞/巨噬细胞流入所需的趋化信号，正如其在体外结合和抑制 CC 趋化因子的能力所预测的那样。 (C) 1999 年学术出版社。
Myxoma virus is a poxvirus that causes a virulent systemic disease called myxomatosis in European rabbits. Like many poxviruses, myxoma Virus encodes a variety of secreted proteins that subvert the antiviral activities of host cytokines. It was recently demonstrated that the myxoma virus M-T1 glycoprotein is a member of a large poxvirus family of secreted proteins that bind CC-chemokines and inhibit their chemoattractant activities in vitro. To determine the biological role of M-T1 in contributing to myxoma virus virulence, we constructed a recombinant M-T1-deletion mutant Virus that was defective in M-T1 expression. Here, we demonstrate that M-T1 is expressed continuously during the course of myxoma virus infection as a highly stable 43-kDa glycoprotein and is dispensable for virus replication in vitro. Deletion of M-T1 had no significant effects on disease progression or in the overall mortality rate of infected European rabbits but heightened the localized cellular inflammation in primary tissue sites during the initial 2 to 3 days of infection. In the absence of M-T1 expression, deep dermal tissues surrounding the primary site of virus inoculation showed a dramatic increase in infiltrating leukocytes, particularly monocytes/macrophages, but these phagocytes remained relatively ineffective at clearing virus infection, likely due to the concerted properties of other secreted myxoma virus proteins. We conclude that M-T1 inhibits the chemotactic signals required for the influx of monocytes/macrophages during the acute-phase response of myxoma virus infection in vivo, as predicted by its ability to bind and inhibit CC-chemokines in vitro. (C) 1999 Academic Press.