Immunology of the Coxsackieviruses

The coxsackieviruses are the best-studied group of nonpolio enteroviruses. Unlike that of the polioviruses, the immune reactions of the human or murine (in models of human disease) hosts of infections by the coxsackieviruses are an important component of the diseases generally induced by these viruses. The first T-cell epitope of the coxsackieviruses to be recognized is located in the 2C protein and is held in common with other human enteroviruses; the predominant lymphocyte population proliferating in response to the 2C epitope was CD4+ T cells. In a study using the CVB4-induced murine pancreatitis model, CVB4-inoculated nude and severe combined immunodeficient SCID mice had increased viral replication in the pancreas and increased mortality at early stages of disease, but CD4 knockout mice were protected. This work suggests that CD4+ T-cell responses in the pancreas (a tissue which, in intraperitoneally inoculated mice, achieves coxsackievirus titers as high or higher and more rapidly than serum titers observed in viremia) may be essential for survival during early virus-induced disease, but at later times these cells participate in increased inflammatory disease. In conclusion, immune responses against coxsackieviruses have been explored through the use of murine models of virus-induced heart and pancreatic diseases. The diversity of inbred mouse lines and viral strains leaves the significance of studies to be resolved by comparison with human disease or by a methodical dissection of the immune response to coxsackieviruses generated in the various murine strains.