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

Abstract

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.

Human cancer cells have specifically lost the ability to induce the synergistic state caused by tumor necrosis factor plus interferon-β

“…Consistent with the hypothesis that abrogation of the ability to induce the TNF/IFNβ synergistic state is a prerequisite for cellular immortalization and/or transformation, all previous reports describing TNF/IFNβ synergistic responses have been performed only in primary cells, such as human macrophages [10], human fibroblasts [8,11], or rat neuronal cells [12]. Interestingly, there is a large body of literature demonstrating that TNF can also synergize with IFNγ, but this synergistic state is demonstrably different from that induced by TNF plus type I IFN [13].…”

Vaccination of pigs against pseudorabies virus with plasmid DNA encoding glycoprotein D

“…MHC class II restricted T-cells, may also be involved in the cytotoxic response which restricts viral replication [36]. Moreover, these CD4 + T-cells may inhibit viral replication by production of cytokines with antiviral activity, such as IFN-g [37]. CD4 + T-cells have been implicated in the resistance against another alphaherpes virus, herpes simplex virus (HSV); Manickan et al [7] demonstrated that in mice immunized with HSV-gB DNA, a CD4 + T-cell response protected the animals from infection with HSV-1.…”

Late phase inhibition of murine cytomegalovirus replication by synergistic action of interferon-gamma and tumour necrosis factor

“…Among DNA viruses~ adenovirus (Wong et al, 1986;Mayer et al, 1992), African swine fever virus (Esparza et al, 1988), and the alphaherpesviruses HSV (Wong et al, 1986;Feduchi et al, 1989) and pseudorabies virus (Schijns et al, 1991) have been found to be susceptible to this combination of cytokines. Here we report that the replication of MCMV, a betaherpesvirus, is also susceptible to their synergistic action.…”

“…Another possibility, not mutually exclusive of the former, is that IFNp must associate with other cytokines to exhibit a direct antiviral effect. It has been reported that turnout necrosis factor (TNF) and IFN-~ in combination have synergistic antiviral activity against DNA viruses such as adenovirus type 2 (Mayer et al, 1992;Wong & Goeddel, 1986), herpes simplex virus type 1 (HSV-1) (Feduchi et al, 1989) and HSV-2 (Wong & Goeddel, 1986) and pseudorabies virus (Schijns et al, 1991). The TNFs 0~ and fl (TNF-~/fl) are synthesized by monocytes and lymphocytes respectively, bind to the same receptor and have indistinguishable biologica/ activities (Aggarwal et al, 1985;Beutler & Cerami, 1989;Paul & Ruddle, 1988).…”