Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, United States.
Virus Res. 2013 Dec 26;178(2):281-6. doi: 10.1016/j.virusres.2013.09.030. Epub 2013 Oct 4.
The normally asymptomatic human polyomavirus, JCPyV, is the causative agent of a rare but fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). Individuals at risk for developing PML include those with AIDS, with other underlying immunosuppressive diseases, and in patients treated with immunomodulatory regimens. Drugs to prevent viral reactivation in the setting of immunosuppression or immunomodulation could be used to sustain lives. Development of such drugs has been impeded by the difficulty of growing and studying the virus. We sought to develop a more efficient method for screening drugs that inhibit viral infection. Pseudovirus models have been developed which may be of use in pharmaceutical research. The use of pseudoviruses as models for viral infection is dependent on them using similar pathways for infection as virus. We screened known inhibitors of viral entry for their ability to block pseudovirus infection. Here we show that the pseudovirus based on the human polyomavirus JCPyV recapitulates virus binding, entry and trafficking. This system can be used for high-throughput screening of antiviral drugs.
通常无症状的人类多瘤病毒 JCPyV 是一种罕见但致命的脱髓鞘疾病进行性多灶性白质脑病 (PML) 的病原体。有发生 PML 风险的个体包括艾滋病患者、有其他潜在免疫抑制性疾病的患者,以及接受免疫调节治疗方案的患者。在免疫抑制或免疫调节的情况下,预防病毒再激活的药物可用于维持生命。然而,由于病毒生长和研究的困难,此类药物的开发受到了阻碍。我们试图开发一种更有效的方法来筛选抑制病毒感染的药物。已开发出假病毒模型,这些模型可能在药物研究中有用。假病毒作为病毒感染模型的使用取决于它们是否使用类似的感染途径。我们筛选了已知的病毒进入抑制剂,以检测它们抑制假病毒感染的能力。在这里,我们展示了基于人类多瘤病毒 JCPyV 的假病毒可以重现病毒结合、进入和转运。该系统可用于抗病毒药物的高通量筛选。