Alpha and gamma interferons inhibit herpes simplex virus type 1 infection and spread in epidermal cells after axonal transmission

The ability of alpha interferon (IFN-alpha) and IFN-gamma to inhibit transm ission of herpes simplex virus type I (HSV-1) from neuronal axon to epiderm al cells (ECs), and subsequent spread in these cells was investigated in an in vitro dual-chamber model consisting of human fetal dorsal root ganglia (DRG) innervating autologous skin explants and compared with direct HSV-1 i nfection of epidermal explants. After axonal transmission from HSV-1-infect ed DRG neurons, both the number and size of viral cytopathic plaques in ECs was significantly reduced by addition of recombinant IFN-gamma and IFN-alp ha to ECs in the outer chamber in a concentration-dependent fashion. Inhibi tion was maximal when IFNs were added at the same time as the DRG were infe cted with HSV-1. The mean numbers of plaques were reduced by 52% by IFN-alp ha, 36% by IFN-gamma, and by 62% when IFN-alpha and IFN-gamma were combined , and the mean plaque size was reduced by 64, 43, and 72%, respectively. Si milar but less-inhibitory effects of both IFNs were observed after direct i nfection of EC explants, being maximal when IFNs were added simultaneously or 6 h before HSV-1 infection. These results show that both IFN-alpha and I FN-gamma can interfere with HSV-1 infection after axonal transmission and s ubsequent spread of HSV-1 in ECs by a direct antiviral effect. Therefore, b oth IFN-alpha and -gamma could contribute to the control of HSV-1 spread an d shedding in a similar fashion in recurrent herpetic lesions.