The proteasome inhibitor Velcade enhances rather than reduces disease in mouse hepatitis coronavirus-infected mice

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 s...

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Bibliographic Details
Published in:Journal of virology Vol. 84; no. 15; p. 7880
Main Authors: Raaben, Matthijs, Grinwis, Guy C M, Rottier, Peter J M, de Haan, Cornelis A M
Format: Journal Article
Language:English
Published: United States 01.08.2010
Subjects:
Animals
Antiviral Agents - therapeutic use
Boronic Acids - therapeutic use
Bortezomib
Coronavirus Infections - drug therapy
Coronavirus Infections - virology
Hepatitis, Viral, Animal - drug therapy
Hepatitis, Viral, Animal - pathology
Hepatitis, Viral, Animal - virology
Mice
Mice, Inbred C57BL
Murine hepatitis virus - drug effects
Murine hepatitis virus - pathogenicity
Protease Inhibitors - therapeutic use
Pyrazines - therapeutic use
Survival Analysis
ISSN:1098-5514, 1098-5514
Online Access:Get more information
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Summary: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.
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ISSN:1098-5514
1098-5514
DOI:10.1128/JVI.00486-10