Persistent expression of chemokine and chemokine receptor RNAs at primary and latent sites of herpes simplex virus 1 infection.
Persistent expression of chemokine and chemokine receptor RNAs at primary and latent sites of herpes simplex virus 1 infection.
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DOI：
10.1186/1743-422x-1-5
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发表时间：
2004-09-23
期刊：
影响因子：
4.8
通讯作者：
Knipe DM
中科院分区：
文献类型：
--
作者：
Cook WJ;Kramer MF;Walker RM;Burwell TJ;Holman HA;Coen DM;Knipe DM
在感染的急性期，在单纯疱疹病毒（HSV）感染的小鼠角膜和三叉神经节（TG）中容易检测到炎性细胞因子和浸润性T细胞，并且在随后的潜伏期，某些细胞因子在感染的TG中继续以较低水平表达。最近的研究结果表明，HSV感染激活Toll样受体信号传导。因此，我们假设趋化因子可能广泛表达在HSV感染的原发部位和潜伏部位，持续时间较长。实时逆转录酶-聚合酶链反应（RT-PCR）定量角膜感染后角膜和TG中编码趋化因子及其受体的转录物的表达水平。编码炎症型趋化因子受体CCR 1、CCR 2、CCR 5和CXCR 3的RNA在活化的T细胞、巨噬细胞和大多数未成熟树突状细胞（DC）上高度表达，以及更广泛表达的CCR 7在感染后3天和10天（dpi）在感染的角膜和TG中高度表达和强烈诱导。在30 dpi的潜伏期期间，这些RNA的水平升高持续存在于角膜和TG中。在角膜和TG中，广泛表达的CXCR 4受体的RNA在30 dpi时被诱导，但在3和10 dpi时较少。在活化的T细胞或巨噬细胞上不高度表达的受体CCR 3和CCR 6的转录物似乎也在急性和潜伏期被诱导;然而，它们非常低的表达水平接近我们的检测极限。编码CCR 1和CCR 5趋化因子配体MIP-1α、MIP-1β和RANTES以及CCR 2配体MCP-1的RNA在潜伏期也被强烈诱导并持续存在于角膜和TG中。这些和其他最近的结果认为，HSV抗原或DNA可以刺激表达的趋化因子，可能通过激活Toll样受体，在很长一段时间内在HSV感染的原发和潜伏部位。这些趋化因子募集活化的T细胞和其他免疫细胞，包括DC，其表达趋化因子受体至感染的原发和继发部位。趋化因子表达的延长激活可以为HSV生物学和发病机制的某些方面提供机制解释。
Inflammatory cytokines and infiltrating T cells are readily detected in herpes simplex virus (HSV) infected mouse cornea and trigeminal ganglia (TG) during the acute phase of infection, and certain cytokines continue to be expressed at lower levels in infected TG during the subsequent latent phase. Recent results have shown that HSV infection activates Toll-like receptor signaling. Thus, we hypothesized that chemokines may be broadly expressed at both primary sites and latent sites of HSV infection for prolonged periods of time. Real-time reverse transcriptase-polymrease chain reaction (RT-PCR) to quantify expression levels of transcripts encoding chemokines and their receptors in cornea and TG following corneal infection. RNAs encoding the inflammatory-type chemokine receptors CCR1, CCR2, CCR5, and CXCR3, which are highly expressed on activated T cells, macrophages and most immature dendritic cells (DC), and the more broadly expressed CCR7, were highly expressed and strongly induced in infected cornea and TG at 3 and 10 days postinfection (dpi). Elevated levels of these RNAs persisted in both cornea and TG during the latent phase at 30 dpi. RNAs for the broadly expressed CXCR4 receptor was induced at 30 dpi but less so at 3 and 10 dpi in both cornea and TG. Transcripts for CCR3 and CCR6, receptors that are not highly expressed on activated T cells or macrophages, also appeared to be induced during acute and latent phases; however, their very low expression levels were near the limit of our detection. RNAs encoding the CCR1 and CCR5 chemokine ligands MIP-1α, MIP-1β and RANTES, and the CCR2 ligand MCP-1 were also strongly induced and persisted in cornea and TG during the latent phase. These and other recent results argue that HSV antigens or DNA can stimulate expression of chemokines, perhaps through activation of Toll-like receptors, for long periods of time at both primary and latent sites of HSV infection. These chemokines recruit activated T cells and other immune cells, including DC, that express chemokine receptors to primary and secondary sites of infection. Prolonged activation of chemokine expression could provide mechanistic explanations for certain aspects of HSV biology and pathogenesis.