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 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.
Raaben
Matthijs
M
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Grinwis
Guy C M
GC
Rottier
Peter J M
PJ
de Haan
Cornelis A M
CA
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D018352:Coronavirus Infections / Q000188:drug therapy* / Q000821:virology; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000187:drug effects* / Q000472:pathogenicity; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D016019:Survival Analysis
D000998:Antiviral Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib