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 transmission of herpes simplex virus type 1 (HSV-1) from neuronal axon to epidermal 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 infection of epidermal explants. After axonal transmission from HSV-1-infected DRG neurons, both the number and size of viral cytopathic plaques in ECs was significantly reduced by addition of recombinant IFN-gamma and IFN-alpha to ECs in the outer chamber in a concentration-dependent fashion. Inhibition was maximal when IFNs were added at the same time as the DRG were infected with HSV-1. The mean numbers of plaques were reduced by 52% by IFN-alpha, 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. Similar but less-inhibitory effects of both IFNs were observed after direct infection 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 IFN-gamma can interfere with HSV-1 infection after axonal transmission and subsequent spread of HSV-1 in ECs by a direct antiviral effect. Therefore, both IFN-alpha and -gamma could contribute to the control of HSV-1 spread and shedding in a similar fashion in recurrent herpetic lesions.
Mikloska
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Centre for Virus Research, Westmead Millennium Institute, Westmead Hospital and University of Sydney, Westmead, New South Wales 2145, Australia.
Cunningham
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D001369:Axons / Q000821:virology*; D046508:Culture Techniques; D003588:Cytopathogenic Effect, Viral / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
D016898:Interferon-alpha; D007371:Interferon-gamma