Cytomegalovirus-encoded beta chemokine promotes monocyte-associated viremia in the host.

Cytomegalovirus-encoded beta chemokine promotes monocyte-associated viremia in the host.
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巨细胞病毒编码的β趋化因子促进宿主中单核细胞相关的病毒血症。

DOI:
10.1073/pnas.96.19.10881
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发表时间:
1999
影响因子:
11.1
通讯作者:
Mocarski,ES
Mocarski,ES
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Saederup,N;Lin,YC;Dairaghi,DJ;Schall,TJ;Mocarski,ES

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趋化因子同源物由许多大的DNA病毒编码,表明它们有助于控制病毒感染期间宿主白细胞的迁移和运输。鼠巨细胞病毒携带CC(β)趋化因子同源基因,产生两种相关蛋白,鼠巨细胞病毒趋化因子1和2(MCK-1和MCK-2)。发现MCK-1肽诱导小鼠腹腔巨噬细胞中的钙信号传导和粘附。携带人趋化因子受体CCR 3的细胞和人巨噬细胞THP 1细胞系对MCK-1有应答。这种模式表明,MCK-1可能作为一种激动剂,促进白细胞运输病毒感染。与这一预测一致,MCK-1/MCK-2突变病毒在实验感染小鼠中表现出单核细胞相关病毒血症的峰值水平显著降低。因此,MCK-1/MCK-2似乎促进宿主白细胞迁移到感染的初始部位,并可能负责吸引单核细胞或巨噬细胞,从而有效地在宿主中传播病毒。
Chemokine homologs are encoded by many large DNA viruses, suggesting that they contribute to control of host leukocyte transmigration and trafficking during viral infection. Murine cytomegalovirus carries a CC (β) chemokine homolog gene giving rise to two related proteins, murine cytomegalovirus chemokine 1 and 2 (MCK-1 and MCK-2). MCK-1 peptide was found to induce calcium signaling and adherence in murine peritoneal macrophages. Cells bearing human chemokine receptor CCR3 and the human macrophage THP1 cell line were responsive to MCK-1. This pattern suggested that MCK-1 might act as an agonist, promoting leukocyte trafficking during viral infection. Consistent with this prediction, MCK-1/MCK-2 mutant viruses exhibit dramatically reduced peak levels of monocyte-associated viremia in experimentally infected mice. Thus, MCK-1/MCK-2 appears to promote host leukocyte migration to initial sites of infection and may be responsible for attracting monocytes or macrophages that efficiently disseminate virus in the host.
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