Comparison of the effects of rabies virus infection and of combined interferon and poly(I).poly(C) treatment on the levels of 2',5'-adenyladenosine oligonucleotides in different organs of mice.

Abstract

Intracellular levels of 2',5'-adenyladenosine oligonucleotides were analyzed in different organs of mice during the course of a rabies virus infection. Phosphorylated and nonphosphorylated 2',5'-adenyladenosine oligonucleotides were measured by radioimmunoassay and analyzed further by HPLC. As the infection progressed, concentrations of phosphorylated 2',5'-adenyladenosine oligonucleotides increased strongly, reaching their maxima late in the infection. In contrast, concentrations of the nonphosphorylated 2',5'-adenyladenosine oligonucleotides decreased. A similar phenomenon was observed in spleens analyzed at intervals after treatment of noninfected mice with interferon and poly(I).poly(C) and to a lesser extent after treatment of noninfected mice with interferon and poly(I).poly(C) and to a lesser extent after treatment with poly(I).poly(C) alone, but not after treatment with interferon alone. The products which accumulated during virus infection were primarily phosphorylated dimers whereas during combined interferon and poly(I).poly(C) treatment, the entire range of phosphorylated molecules from dimer to pentamer was present. These data show that infection of mice with rabies virus provokes both the induction and the activation of 2-5A synthetase, as does interferon and poly(I).poly(C) treatment. However, our data indicate that the intracellular products are different in the two situations: the species active on the nuclease were only detected in interferon- and poly(I).poly(C)-treated mice. The absence of molecules able to activate the 2-5A-dependent nuclease in virus-infected mice might well be one of the reasons why the interferon system is ineffective in rabies virus infection.