Cytokines and costimulatory molecules in the immune response to murine gammaherpesvirus-68.
Murine gammaherpesvirus 68 (MHV-68) infection of mice provides a useful small animal model for studying gammaherpesvirus pathogenesis and immunity. Recent work has elucidated the cytokine and chemokine profiles during MHV-68 infection and has identified some of the costimulatory interactions that are important for an effective immune response to this virus. Several themes emerge from this work. There is a differential requirement for certain cytokines and costimulatory molecules in the acute and long-term control of MHV-68, and for control of the virus in different anatomical sites. CD4 T cell help is not required for short-term control of MHV-68 in the lung by cytotoxic CD8 T cells, but is essential for effective long-term control. Stimulation via CD40 is an important component of this CD4 T cell help, and interestingly, some of its effects appear to be independent of CD28. MHV-68 infection also increases the expression of several chemokines, which could potentially play important roles in leukocyte trafficking to sites of infection. However, to counter this response, MHV-68 has evolved strategies that enable it to evade or subvert the host chemokine system. Studying the role of cytokines and costimulatory molecules in immunity to MHV-68 may provide useful insights for the development of agents to control gammaherpesviruses that cause human disease.
Sarawar
Sally R
SR
Torrey Pines Institute for Molecular Studies, San Diego, California, USA. ssarawar@tpims.org
Lee
Bong Joo
BJ
Giannoni
Francesca
F
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D018142:Gammaherpesvirinae / Q000472:pathogenicity*; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018106:CD28 Antigens; D019013:CD40 Antigens; D016207:Cytokines; D023201:CD40 Ligand