Alternatively spliced soluble coxsackie-adenovirus receptors inhibit coxsackievirus infection
Alternatively spliced soluble coxsackie-adenovirus receptors inhibit coxsackievirus infection
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DOI：
10.1074/jbc.m311754200
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发表时间：
2004-04-30
影响因子：
4.8
通讯作者：
Knowlton, KU
中科院分区：
文献类型：
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作者：
Dörner, A;Xiong, DD;Knowlton, KU
柯萨奇-腺病毒受体（CAR）是免疫球蛋白超家族的跨膜受体，其表达在心肌和恶性疾病中改变。其他粘附分子和细胞因子受体的可溶性同种型已被证明对其全长受体具有显著的激动剂和拮抗剂作用;然而，对可溶性CAR受体知之甚少。使用逆转录-PCR，我们鉴定了三种CAR同种型，其缺乏跨膜结构域并且是外显子IV和VII（CAR 4/7）、外显子III和VII（CAR 3/7）以及外显子II和VII（CAR 2/7）之间的选择性RNA剪接事件的结果。三种CAR同种型含有CAR的胞外结构域的不同区域，并且具有与全长受体不同的C末端。这些选择性剪接的CAR蛋白从转染的HeLa细胞中释放，证实它们是可溶性蛋白。此外，可溶性CAR蛋白能够与细菌表达的CAR胞外结构域相互作用。此外，发现CAR 4/7而不是CAR 2/7与柯萨奇病毒B3（CVB 3）结合。三种可溶性CAR同种型中的每一种都能够抑制转染的HeLa细胞的CVB 3感染。鉴于可溶性CAR同种型可以结合CAR的胞外结构域和CVB 3衣壳，它们可能对CAR信号传导具有显著的抑制或刺激作用，并且可能在宿主防御病毒感染中具有重要作用。
The coxsackie-adenovirus receptor (CAR) is a transmembrane receptor of the immunoglobulin superfamily whose expression is altered in myocardial and malignant diseases. Soluble isoforms of other adhesion molecules and cytokine receptors have been proven to have significant agonist and antagonist effects on their full-length receptors; however, little is known about soluble CAR receptors. Using reverse transcription-PCR, we identified three CAR isoforms that lack the transmembrane domain and are the result of alternative RNA splicing events between exons IV and VII (CAR4/7), exons III and VII (CAR3/7), and exons II and VII (CAR2/7). The three CAR isoforms contain different regions of the extracellular domain of CAR and have C termini that are distinct from the full-length receptors. These alternatively spliced CAR proteins are released from transfected HeLa cells confirming that they are soluble proteins. In addition, the soluble CAR proteins are able to interact with the bacterially expressed extracellular domain of CAR. In addition, CAR4/7 but not CAR2/7 was found to bind to coxsackievirus B3 (CVB3). Each of the three soluble CAR isoforms is able to inhibit CVB3 infection of transfected HeLa cells. Given that soluble CAR isoforms can bind to the extracellular domain of CAR and the CVB3 capsid, they may have significant inhibitory or stimulatory effects on CAR signaling and may have an important role in the host defense against viral infection.