Induction of chemokines in human astrocytes by picornavirus infection requires activation of both AP-1 and NF-kappa B.

Infection with different picornaviruses can cause meningitis/encephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astrocytes was investigated following infection with Theiler's murine encephalomyelitis virus (TMEV), coxsackievirus B3 (CVB3), or coxsackievirus B4 (CVB4). We report that all these viruses are potent inducers for the expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) genes in primary human astrocytes, as well as in an established astrocyte cell line (U-373MG). Further studies indicated that both activator protein-1 (AP-1) and NF-kappaB transcription factors are required in the activation of chemokine genes in human astrocytes infected with various picornaviruses. Interestingly, the pattern of activated chemokine genes in human astrocytes is quite restricted compared to that in mouse astrocytes infected with the same viruses, suggesting species differences in gene activation. This may result in potential differences in the pathogenic outcome in each species.