Treatment of Wag/Rij rats with recombinant rat interferon gamma (rRIF-γ) resulted in complete protection against a lethal pseudorabies virus (PRV) infection. To investigate whether the protection resulted from direct inhibition of virus replication or from a stimulation of immune mechanisms, we tested rRIF-γ activity in naturally immunocompromised and artificially immunosuppressed rats. The antiviral effect of rRIF-γ was not abolished in silica- and carrageenan-treated, phagocyte-depleted rats. Immunologically immature newborn and T cell-deficient nude rats were also protected under a regime of rRIF-γ treatment as well as whole body gamma-irradiated rats. Sera of the protected rats were devoid of PRV-neutralizing antibodies. Our results indicate that the protective activity of rRIF-γ is based on direct inhibition of virus replication; stimulation of the immune system is not required but may be responsible for protection upon challenge several weeks after infection.


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