蛋白酶体抑制剂硼替佐米增强而非减轻感染鼠肝炎冠状病毒的小鼠的疾病。
The proteasome inhibitor Velcade enhances rather than reduces disease in mouse hepatitis coronavirus-infected mice.
机构信息
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
出版信息
J Virol. 2010 Aug;84(15):7880-5. doi: 10.1128/JVI.00486-10. Epub 2010 May 19.
Abstract
Many viruses, including coronaviruses (CoVs), depend on a functional cellular proteasome for efficient infection in vitro. Hence, the proteasome inhibitor Velcade (bortezomib), a clinically approved anticancer drug, shown in an accompanying study (M. Raaben et al., J. Virol. 84:7869-7879, 2010) to strongly inhibit mouse hepatitis CoV (MHV) infection in cultured cells, seemed an attractive candidate for testing its antiviral properties in vivo. Surprisingly, however, the drug did not reduce replication of the virus in mice. Rather, inhibition of the proteasome caused enhanced infection with lethal outcome, calling for caution when using this type of drug during infection.
摘要
许多病毒，包括冠状病毒（CoV），在体外感染中依赖于功能性的细胞蛋白酶体。因此，蛋白酶体抑制剂硼替佐米（Velcade），一种已在临床中被批准的抗癌药物，在一项伴随研究中显示（M. Raaben 等人，J. Virol. 84:7869-7879, 2010）能强烈抑制细胞培养中的小鼠肝炎冠状病毒（MHV）感染，似乎是一种具有吸引力的候选药物，可在体内测试其抗病毒特性。然而，令人惊讶的是，该药物并没有降低病毒在小鼠体内的复制。相反，蛋白酶体的抑制导致感染增强并导致致命后果，因此在感染期间使用此类药物时需要谨慎。
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