The ubiquitin-proteasome machinery is essential for nuclear translocation of incoming minute virus of mice.
Minute virus of mice (MVM) infection is disrupted by proteasome inhibitors. Here, we show that inhibition of the ubiquitin-proteasome pathway did not affect viral entry and had influence neither on the natural proteolytic cleavage of VP2 to VP3 nor on the externalization of the N terminal of VP1. In both MG132-treated and untreated cells, MVM particles accumulated progressively in the perinuclear region. However, in MG132-treated cells, MVM was not able to penetrate into the nuclei, remaining blocked in the perinuclear region without capsid disassembly. MVM was similarly sensitive to MG132 in the two cell lines tested, A9 and NB324K. After releasing from the reversible MG132 block, MVM recovered the ability to translocate to the nuclei and replicate. Analysis of viral capsid proteins during internalization showed no evidence of capsid ubiquitination or degradation. We examined the effect of MG132 on two other parvoviruses, canine (CPV) and bovine parvovirus (BPV). Similarly to MVM, CPV infection was sensitive to MG132; however, BPV infection, as previously shown for adeno-associated viruses (AAVs), was not disturbed. These findings suggest that parvoviruses follow divergent strategies for nuclear transport, some of them requiring active proteasomes.
Ros
Carlos
C
Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland. carlos.ros@ibc.unibe.ch
Kempf
Christoph
C
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002213:Capsid / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D042541:Intracellular Space / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D008915:Minute Virus of Mice / Q000187:drug effects / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D013997:Time Factors; D025801:Ubiquitin / Q000378:metabolism*; D014779:Virus Replication
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009097:Multienzyme Complexes; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde