人类多瘤病毒JCV利用血清素受体感染细胞。

The human polyomavirus, JCV, uses serotonin receptors to infect cells.

作者信息

Elphick Gwendolyn F, Querbes William, Jordan Joslynn A, Gee Gretchen V, Eash Sylvia, Manley Kate, Dugan Aisling, Stanifer Megan, Bhatnagar Anushree, Kroeze Wesley K, Roth Bryan L, Atwood Walter J

机构信息

Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.

出版信息

Science. 2004 Nov 19;306(5700):1380-3. doi: 10.1126/science.1103492.

DOI:10.1126/science.1103492

PMID:15550673

Abstract

The human polyomavirus, JCV, causes the fatal demyelinating disease progressive multifocal leukoencephalopathy in immunocompromised patients. We found that the serotonergic receptor 5HT2AR could act as the cellular receptor for JCV on human glial cells. The 5HT2A receptor antagonists inhibited JCV infection, and monoclonal antibodies directed at 5HT2A receptors blocked infection of glial cells by JCV, but not by SV40. Transfection of 5HT2A receptor-negative HeLa cells with a 5HT2A receptor rescued virus infection, and this infection was blocked by antibody to the 5HT2A receptor. A tagged 5HT2A receptor colocalized with labeled JCV in an endosomal compartment following internalization. Serotonin receptor antagonists may thus be useful in the treatment of progressive multifocal leukoencephalopathy.

摘要

人多瘤病毒JCV可在免疫功能低下的患者中引发致命的脱髓鞘疾病——进行性多灶性白质脑病。我们发现，血清素能受体5HT2AR可作为JCV在人神经胶质细胞上的细胞受体。5HT2A受体拮抗剂可抑制JCV感染，针对5HT2A受体的单克隆抗体可阻断JCV对神经胶质细胞的感染，但对SV40感染无效。用5HT2A受体转染5HT2A受体阴性的HeLa细胞可恢复病毒感染，且这种感染可被针对5HT2A受体的抗体阻断。内化后，带有标签的5HT2A受体与标记的JCV在内体区室中共定位。因此，血清素受体拮抗剂可能对进行性多灶性白质脑病的治疗有用。