The immunoproteasome is protective during acute murine hepatitis virus respiratory infection but dispensable for adaptive immunity.

Abstract

The immunoproteasome (IP) is a component of cellular proteasome machinery that is predominantly inducible by IFN-γ. IP activity contributes to multiple aspects of immune function, inflammation, and protein homeostasis. IP subunit expression increases during respiratory infection with murine hepatitis virus strain 1 (MHV-1), a mouse coronavirus, and pharmacologic inhibition increased virus-induced inflammation and mortality. In this study, we used mice that are completely deficient in IP activity to evaluate effects of IP deficiency, instead of IP inhibition, on MHV-1 pathogenesis. IP deficiency had no effect on viral replication in lungs or livers in mice infected with a low dose, but viral replication was greater in livers of mice infected with a high dose. IP deficiency altered expression of IFN-γ and other cytokines in an organ- and virus dose-dependent manner. MHV-1 infection increased expression of genes associated with endoplasmic reticulum stress response, but there were minimal differences between IP-deficient and wild type mice. IP deficiency tended to decrease the amount of total virus-specific IgG. However, neutralizing antibody and protective immunity to repeat MHV-1 infection was intact in IP-deficient mice. Our results indicate that the IP is a protective host factor during acute MHV-1 infection, confirming our previous findings with IP inhibition. However, the results suggest that the IP is dispensable for the development of adaptive immune responses and protective immunity to MHV-1.