The role of the proteasome–ubiquitin pathway in regulation of the IFN-γ mediated anti-VSV response in neurons

Pharmacologic inhibition of the proteasome resulted in increased NOS-1 protein levels and increased NO production by neuronal cells. This correlated with an increased antiviral effect of IFN-γ against the replication of vesicular stomatitis virus (VSV) replication in vitro. We also observed that a regulatory protein, Protein Inhibitor of NOS-1 (PIN) was down-regulated by IFN-γ treatment, and more ubiquitinated PIN accumulated in IFN-γ treated neurons. In cells of the reticuloendothelial system, IFN-γ treatment induces the expression of a set of low molecular weight MHC-encoded proteins (LMPs), which replace the β-subunit of the proteasome complex during the proteasome neosynthesis, resulting in a complex termed the immunoproteasome. LMP2, -7, and -10 were induced and the immunoproteasome was generated by IFN-γ treatment in neuronal cells. Importantly, we observed that IFN-γ induced inhibition of VSV protein synthesis was not dependent on ubiquitination.