Integrins α2β1 and α4β1 can mediate SA11 rotavirus attachment and entry into cells
Integrins α2β1 and α4β1 can mediate SA11 rotavirus attachment and entry into cells
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DOI：
10.1128/jvi.74.1.228-236.2000
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发表时间：
2000-01-01
影响因子：
5.4
通讯作者：
Coulson, BS
中科院分区：
文献类型：
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作者：
Hewish, MJ;Takada, Y;Coulson, BS
大多数哺乳动物轮状病毒在外衣壳蛋白VP 4和VP 7中含有三肽氨基酸序列，其已显示作为整联蛋白α 2 β 1和α 4 β 1的配体。含有这些序列的肽和针对这些整联蛋白的单克隆抗体阻断轮状病毒对细胞的感染。在这里，我们报告说，SA 11轮状病毒结合和感染的K562细胞表达α 2 β 1或α 4 β 1整合素通过转染增加了病毒结合和感染的细胞转染α 3整合素或亲本细胞。增加的结合和生长仅仅被转染的整合素亚基的单克隆抗体特异性阻断，而不是被无关抗体阻断。在我们的实验中，用佛波醇酯活化整联蛋白不影响病毒与细胞的结合。然而，佛波酯处理K562亲本和转染细胞诱导内源性基因表达的α 2 β 1整合素，这是可检测的流式细胞术治疗后16小时，并定量相关的增加水平的SA 11病毒生长后观察到的时间。与对照细胞结合相比，病毒与先前用佛波酯处理24小时并表达α 2 β 1的K562细胞的结合升高，并被抗α 2单克隆抗体AK 7特异性阻断。在α 4-转染的K562细胞中，病毒生长也被诱导表达α 2 β 1整联蛋白与佛波酯，发生在一个接近的水平，在允许的MA 104细胞系。因此，我们已经证明了两种整合素，α 2 β 1和α 4 β 1，能够作为SA 11轮状病毒的细胞受体。
Most mammalian rotaviruses contain tripeptide amino acid sequences in outer capsid proteins VP4 and VP7 which have been shown to act as ligands for integrins alpha 2 beta 1 and alpha 4 beta 1. Peptides containing these sequences and monoclonal antibodies directed to these integrins block rotavirus infection of cells. Here we report that SA11 rotavirus binding to and infection of K562 cells expressing alpha 2 beta 1 or alpha 4 beta 1 integrins via transfection is increased over virus binding to and infection of cells transfected with alpha 3 integrin or parent cells. The increased binding and growth mere specifically blocked by a monoclonal antibody to the transfected integrin subunit hut not by irrelevant antibodies. In our experiments, integrin activation with phorbol ester did not affect virus binding to cells. However, phorbol ester treatment of K562 parent and transfected cells induced endogenous gene expression of alpha 2 beta 1 integrin, which was detectable by flow cytometry 16 h after treatment and quantitatively correlated with the increased level of SA11 virus growth observed after this time. Virus binding to K562 cells treated with phorbol ester 24 h previously and expressing alpha 2 beta 1 was elevated over binding to control cells and was specifically blocked by the anti-alpha 2 monoclonal antibody AK7. Virus growth in alpha 4-transfected K562 cells which had also been induced to express alpha 2 beta 1 integrin with phorbol ester occurred at a level approaching that in the permissive MA104 cell line. We therefore have demonstrated that two integrins, alpha 2 beta 1 and alpha 4 beta 1, are capable of acting as cellular receptors for SA11 rotavirus.