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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.

DOI:10.1128/JVI.00486-10
PMID:20484516
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2897637/
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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本文引用的文献

1
The ubiquitin-proteasome system plays an important role during various stages of the coronavirus infection cycle.泛素-蛋白酶体系统在冠状病毒感染周期的各个阶段都起着重要作用。
J Virol. 2010 Aug;84(15):7869-79. doi: 10.1128/JVI.00485-10. Epub 2010 May 19.
2
The proteasome inhibitor bortezomib enhances the susceptibility to viral infection.蛋白酶体抑制剂硼替佐米增强了对病毒感染的易感性。
J Immunol. 2009 Nov 15;183(10):6145-50. doi: 10.4049/jimmunol.0901596. Epub 2009 Oct 19.
3
Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo.体内小鼠肝炎冠状病毒感染的I型干扰素受体非依赖性和依赖性宿主转录反应
BMC Genomics. 2009 Aug 3;10:350. doi: 10.1186/1471-2164-10-350.
4
Proteasome inhibition induces apoptosis in primary human natural killer cells and suppresses NKp46-mediated cytotoxicity.蛋白酶体抑制可诱导原代人自然杀伤细胞凋亡,并抑制NKp46介导的细胞毒性。
Haematologica. 2009 Apr;94(4):470-8. doi: 10.3324/haematol.13783. Epub 2009 Feb 19.
5
Non-invasive imaging of mouse hepatitis coronavirus infection reveals determinants of viral replication and spread in vivo.利用非侵入性成像技术研究鼠肝炎冠状病毒感染,揭示了病毒在体内复制和传播的决定因素。
Cell Microbiol. 2009 May;11(5):825-41. doi: 10.1111/j.1462-5822.2009.01298.x. Epub 2009 Feb 10.
6
Vorinostat and bortezomib exert synergistic antiproliferative and proapoptotic effects in colon cancer cell models.伏立诺他和硼替佐米在结肠癌细胞模型中发挥协同抗增殖和促凋亡作用。
Mol Cancer Ther. 2009 Feb;8(2):342-9. doi: 10.1158/1535-7163.MCT-08-0534. Epub 2009 Jan 27.
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