Tumour necrosis factor- , interferon-? and interferon-fl exert antiviral activity in nervous tissue cells

The individual and synergistic antiviral effects of cytokines released by infiltrating immune cells or by cells of the nervous system may play an important role in inhibiting virus spread during infections of the central nervous system (CNS). We examined the antiviral activity against the neurotropic pseudorabies virus (PRV) of interferon-y (IFN-y) and tumour necrosis factor-~ (TNF-ct), and combinations of these cytokines, as compared to that of IFN-fl, in rat nervous tissue cells. PRV replicated efficiently in all neural cell types tested, including neurons, astrocytes and oligodendrocytes. The inhibitory effects were determined by quantifying the inhibition of virus plaque formation, yields of infectious virus at various times after infection and synthesis of viral proteins. At a low m.o.i., IFN-), and IFN-fl inhibited viral plaque formation in all cell types; TNF-~ was effective only in astrocytes but showed synergy with IFN-~. At a higher m.o.i., IFN-fl inhibited yields of infectious virus more effectively than IFN-y, whereas TNF-~ had no effect on virus yields and was only marginally synergistic with the antiviral activity of IFN-~. The yield-reduction assays correlated well with cytokine-induced inhibition of viral protein synthesis. Our results show that both IFN-~ and IFN-fl can induce a state of antiviral resistance in neural cells whereas TNF-~ is effective only in astrocytes at low m.o.i.; they suggest an antiviral role of cytokines in the immune response to virus infections of the CNS.