Modulation of RANTES production by human cytomegalovirus infection of fibroblasts

Modulation of RANTES production by human cytomegalovirus infection of fibroblasts
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DOI:
10.1128/jvi.71.9.6495-6500.1997
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发表时间:
1997-09-01
影响因子:
5.4
通讯作者:
Landini, MP
Landini, MP
中科院分区:
医学2区
文献类型:
--
作者:
Michelson, S;DalMonte, P;Landini, MP

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趋化因子在炎症反应中起主要作用,并对造血产生积极和消极的影响。我们发现,新鲜分离株和实验室株(Towne和Ad-169)的人巨细胞病毒(HCMV)诱导生产的CC趋化因子RANTES成纤维细胞。细胞外RANTES的诱导产生早在感染后8 h出现,在感染后24 h左右达到高峰,到48和72 h几乎检测不到。上调发生在病毒DNA合成的情况下,这表明这是由于立即早期早期HCMV基因表达。CMV感染刺激RANTES转录,因为逆转录-PCR检测到RANTES RNA的急剧增加,即使细胞外RANTES不再检测到。成纤维细胞中RANTES的诱导不是由于肿瘤坏死因子α或白细胞介素1 β的预先诱导。下调需要一个活跃的病毒基因组。培养上清液中RANTES的减少可能与HCMV CC趋化因子受体US 28的出现有关,因为我们发现该基因早在感染后8小时就转录。在CMV感染早期,CC趋化因子的产生可能对病毒复制有调节作用,并影响免疫监视。
Chemokines play a major role in inflammatory responses and affect hematopoiesis both negatively and positively. We show that fresh isolates and laboratory strains (Towne and Ad-169) of human cytomegalovirus (HCMV) induce production of the CC chemokine RANTES in fibroblasts. Induction of extracelluIar RANTES production occurred as early as 8 h after infection, peaked around 24 h after infection, and was almost undetectable by 48 and 72 h. Upregulation occurred in the absence of viral DNA synthesis, suggesting that it was due to immediate-early-early HCMV gene expression. CMV infection stimulated RANTES transcription, since reverse transcription-PCR detected a sharp increase in RANTES RNA which persisted even when extracellular RANTES was no longer detected. Induction of RANTES in fibroblasts was not due to prior induction of tumor necrosis factor alpha or interleukin 1 beta. Down-regulation required an active viral genome. Decrease of RANTES in culture supernatants may be associated with the appearance of the HCMV CC chemokine receptor US28, since we show that this gene is transcribed as early as 8 h after infection. Modulation of CC chemokine production early during CMV infection might have a regulatory effect on viral replication, as well as affect immune surveillance.