Regulation of T-type Ca2+ channel expression by interleukin-6 in sensory-like ND7/23 cells post-herpes simplex virus (HSV-1) infection.

Herpes simplex virus-type 1 (HSV-1) infection of sensory neurons may lead to a significant reduction in the expression of voltage-activated Na+ and Ca2+ channels, which can disrupt the transmission of pain information. Viral infection also results in the secretion of various pro-inflammatory cytokines, including interleukin (IL)-6. In this work, we tested whether IL-6 regulates the expression of Na+ and Ca2+ channels post-HSV-1 infection in ND7/23 sensory-like neurons. Our results demonstrate that HSV-1 infection causes a significant decrease in the protein expression of the Cav3.2 T-type Ca2+ channel subunit, despite increasing Cav3.2 mRNA synthesis. Neither Cav3.2 mRNA nor total protein content was affected by IL-6 treatment post-HSV-1 infection. In ND7/23 cells, HSV-1 infection caused a significant reduction in the expression of Na+ and T-type Ca2+ channels within 48 h. Exposure of ND7/23 cells to IL-6 for 24 h post-infection reverses the effect of HSV-1, resulting in a significant increase in T-type Ca2+ current density. However, Na+ currents were not restored by 24-h treatment with IL-6 post-HSV-1 infection of ND7/23 cells. The ability of IL-6 to increase the functional expression of T-type Ca2+ channels on the membrane was blocked by the inhibition of protein trafficking with brefeldin-A and ERK1/2 activation. These results indicate that IL-6 release following HSV-1 infection regulates the expression of T-type Ca2+ channels, which may alter the transmission of pain information.