Protein Kinase C θ Is Not Essential for T-Cell-Mediated Clearance of Murine Gammaherpesvirus 68

Abstract

Murine gammaherpesvirus 68 (MHV-68) is a naturally occurring rodent pathogen with significant homology to human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. T cells are essential for primary clearance of MHV-68 and survival of mice following intranasal infection. Previous reports have suggested that protein kinase C θ (PKCθ) is essential for T-cell activation and cytokine production in vitro. To determine the role of this molecule in vivo during the immune response to a viral infection, PKCθ −/− mice were infected with MHV-68. Despite the essential role of T cells in viral clearance, PKCθ −/− mice survived infection, cleared lytic virus, and maintained effective long-term control of latency. CD8 T-cell expansion, trafficking to the lung, and cytotoxic activity were similar in PKCθ +/+ and PKCθ −/− mice, whereas antiviral antibody and T-helper cell cytokine production were significantly lower in PKCθ −/− mice than in PKCθ +/+ mice. These studies demonstrate a differential requirement for PKCθ in the immune response to MHV-68 and show that PKCθ is not essential for the T-cell activation events leading to viral clearance.