Protein kinase C theta is not essential for T-cell-mediated clearance of murine gammaherpesvirus 68.
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 theta (PKCtheta) 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, PKCtheta-/- mice were infected with MHV-68. Despite the essential role of T cells in viral clearance, PKCtheta-/- 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 PKCtheta+/+ and PKCtheta-/- mice, whereas antiviral antibody and T-helper cell cytokine production were significantly lower in PKCtheta-/- mice than in PKCtheta+/+ mice. These studies demonstrate a differential requirement for PKCtheta in the immune response to MHV-68 and show that PKCtheta is not essential for the T-cell activation events leading to viral clearance.
Giannoni
Francesca
F
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Lyon
Ashley B
AB
Wareing
Mark D
MD
Dias
Peter B
PB
Sarawar
Sally R
SR
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D018142:Gammaherpesvirinae / Q000276:immunology* / Q000472:pathogenicity; D006566:Herpesviridae Infections / Q000201:enzymology* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000074121:Protein Kinase C-theta; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000914:Antibodies, Viral; D016207:Cytokines; D007527:Isoenzymes; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta