Gene expression pattern in Caco-2 cells following rotavirus infection

Gene expression pattern in Caco-2 cells following rotavirus infection
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DOI:
10.1128/jvi.76.9.4467-4482.2002
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发表时间:
2002-05-01
影响因子:
5.4
通讯作者:
Greenberg, HB
Greenberg, HB
中科院分区:
医学2区
文献类型:
--
作者:
Cuadras, MA;Feigelstock, DA;Greenberg, HB

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轮状病毒被认为是全世界婴幼儿严重脱水性腹泻的主要原因。迫切需要采取预防和治疗策略来对抗这种病原体。在组织培养和体内,轮状病毒诱导宿主细胞的结构和功能改变。为了更好地了解轮状病毒感染后事件的分子机制,我们鉴定了感染后mRNA水平发生变化的宿主细胞基因。在这项分析中,我们使用含有超过38,000个人类cdna的微阵列来研究人类肠道细胞系Caco-2对轮状病毒感染的转录反应。我们发现508个基因在轮状病毒感染后16小时受到2倍的差异调节,只有一个基因在感染后1小时受到类似的调节。在这些转录变化中,73%对应于基因的上调,其中大多数发生在感染后12小时或更长时间。根据已知的生物学功能对部分调控基因进行分类,包括编码完整膜蛋白的基因、干扰素调控基因、转录和翻译调控基因以及钙代谢相关基因。提出了感染细胞中全球转录调控的新图景,并讨论了可能参与病毒发病机制的基因家族。
Rotaviruses are recognized as the leading cause of severe dehydrating diarrhea in infants and young children worldwide. Preventive and therapeutic strategies are urgently needed to fight this pathogen. In tissue culture and in vivo, rotavirus induces structural and functional alterations in the host cell. In order to better understand the molecular mechanisms involved in the events after rotavirus infection, we identified host cellular genes whose mRNA levels changed after infection. For this analysis, we used microarrays containing more than 38,000 human cDNAs to study the transcriptional response of the human intestinal cell line Caco-2 to rotavirus infection. We found that 508 genes were differentially regulated >2-fold at 16 h after rotavirus infection, and only one gene was similarly regulated at 1 h postinfection. Of these transcriptional changes, 73% corresponded to the upregulation of genes, with the majority of them occurring late, at 12 or more hours postinfection. Some of the regulated genes were classified according to known biological function and included genes encoding integral membrane proteins, interferon-regulated genes, transcriptional and translational regulators, and calcium metabolism-related genes. A new picture of global transcriptional regulation in the infected cell is presented and families of genes which may be involved in viral pathogenesis are discussed.