Chemokine expression during mouse-hepatitis-virus-induced encephalitis: contributions of the spike and background genes

Abstract

Infection of mice with mouse hepatitis virus (MHV) strain JHM (RJHM) induces lethal encephalitis, with high macrophage and neutrophil, but minimal T-cell, infiltration into the brain when compared to the neuroattenuated strain RA59. To determine if chemokine expression corresponds with the cellular infiltrate, chemokine protein and RNA levels from the brains of infected mice were quantified. RJHM-infected mice had lower T-cell (CXCL9, CXCL10), but higher macrophage-attracting (CCL2), chemokine proteins compared to RA59. RJHM also induced significantly higher CXCL2 (a neutrophil chemoattractant) mRNA compared to RA59. The neurovirulent spike gene chimera SJHM/RA59 induces high levels of T cells and macrophages in the brain compared to the attenuated SA59/RJHM chimera. Accordingly, SJHM/RA59 induced higher levels of CXCL9, CXCL10, and CCL2 protein compared to SA59/RJHM. Chemokine mRNA patterns were in general agreement. Thus, chemokine patterns correspond with the cellular infiltrate, and the spike protein influences levels of macrophage, but not T-cell, chemokines.