No abstract

The requirements for disease development in the mouse epidermal scarification-zosteriform model of HSV infection are likely to parallel those required for primary HSV disease of humans. HSV-1 strains, which are neuroinvasive in the mouse footpad model of HSV encephalitis, caused local site lesions within 3 days and secondary zosteriform lesions along the dermatome within approximately 5 days. HSV-1 strains, which are not neuroinvasive, failed to progress to zosteriform lesion development and local site lesions were mild or absent. Relative differences in the rate and extent of zosteriform lesion development paralleled the behavior of the viruses in the mouse footpad model of neuroinvasion. In conclusion, the viral properties which are important for neuroinvasiveness appear to also determine the ability of an HSV strain to cause zosteriform disease.

UV-inactivated, infectious, and other forms of herpes simplex virus 1 (HSV-1) induced interferon (IFN) production by different routes in myeloid origin mononuclear cells (MOMC) (consisting predominantly of monocytes). GM-CSF activated the MOMC (G-MOMC) to produce greater amounts of interferon while differentiation to DC, by the addition of granulocyte macrophage colony stimulating factor (GM-CSF) and calcium ionophore (GA-MOMC), reduced the levels of interferon production upon challenge with some HSV strains. UV-inactivated virus induced more interferon than infectious virus. L-fucose, an antagonist of the mannose receptor, inhibited the induction of IFN-alpha by UV-inactivated virus and gB(-) virus (defective in penetration) in MOMC and GA-MOMC but not G-MOMC. L-fucose had little effect on interferon induction by infectious HSV-1. The insensitivity of the G-MOMC to fucose inhibition distinguishes these interferon producing cells from the pDC2 cells previously described as natural interferon producing cells. The mannose receptor appears to be involved in the response to non-infectious forms of HSV but infectious virus appears to use a different pathway. These studies suggest that non-infectious virions and HSV infected cell debris effectively stimulate monocytes and pre-dendritic cells to produce IFN-alpha to initiate host protection against HSV infection.