人巨细胞病毒感染中肿瘤坏死因子α和神经酰胺的不同信号通路。
Distinct pathways for tumor necrosis factor alpha and ceramides in human cytomegalovirus infection.
作者信息
Allan-Yorke J, Record M, de Préval C, Davrinche C, Davignon J L
机构信息
INSERM U.395, Toulouse, France.
出版信息
J Virol. 1998 Mar;72(3):2316-22. doi: 10.1128/JVI.72.3.2316-2322.1998.
Human cytomegalovirus (HCMV) infection can be fatal to immunocompromised individuals. We have previously reported that gamma interferon and tumor necrosis factor alpha (TNF-alpha) synergistically inhibit HCMV replication in vitro. Ceramides have been described as second messengers induced by TNF-alpha. To investigate the mechanisms involved in the inhibition of HCMV by TNF-alpha, in the present study we have analyzed ceramide production by U373 MG astrocytoma cells and the effects of TNF-alpha versus ceramides on HCMV replication. Our results show that U373 MG cells did not produce ceramides upon incubation with TNF-alpha. Moreover, long-chain ceramides induced by treatment with exogenous bacterial sphingomyelinase inhibited HCMV replication in synergy with TNF-alpha. Surprisingly, short-chain permeant C6-ceramide increased viral replication. Our results show that the anti-HCMV activity of TNF-alpha is independent of ceramides. In addition, our results suggest that TNF-alpha and endogenous long-chain ceramides use separate pathways of cell signalling to inhibit HCMV replication, while permeant C6-ceramide appears to activate a third pathway leading to an opposite effect.
人巨细胞病毒（HCMV）感染对免疫功能低下的个体可能是致命的。我们之前报道过，γ干扰素和肿瘤坏死因子α（TNF-α）在体外协同抑制HCMV复制。神经酰胺已被描述为TNF-α诱导产生的第二信使。为了研究TNF-α抑制HCMV的机制，在本研究中，我们分析了U373 MG星形细胞瘤细胞中神经酰胺的产生以及TNF-α与神经酰胺对HCMV复制的影响。我们的结果表明，U373 MG细胞与TNF-α孵育后不产生神经酰胺。此外，用外源性细菌鞘磷脂酶处理诱导产生的长链神经酰胺与TNF-α协同抑制HCMV复制。令人惊讶的是，短链渗透性C6-神经酰胺增加了病毒复制。我们的结果表明，TNF-α的抗HCMV活性与神经酰胺无关。此外，我们的结果表明，TNF-α和内源性长链神经酰胺利用不同的细胞信号通路抑制HCMV复制，而渗透性C6-神经酰胺似乎激活了第三条导致相反效应的通路。
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