Induction of a large number of the components of the
interferon (IFN) system (IFN genes, their mRNAs, IFN
proteins, IFN receptors, IFN signaling molecules, the IFN response genes, and their effector
proteins) has been studied. Less well studied is the comparative induction of these components in vivo. Induction of IFN by
double-stranded RNA (dsRNA) treatment mimics certain aspects of
viral infection and induces the components of the IFN system. To determine the comparative sensitivity of detection of induction in mice, we initially studied the limiting concentrations of polyribinosinic-polyribocytidylic
acid,
polylysine complex (
poly I:CLC, a synthetic dsRNA preparation), for induction of four representative components of the IFN system: (1) IFN in serum, (2) the IFN response gene
mRNA ISG54 in spleen and liver, (3) the IFN-beta
mRNA in spleen, and (4) resistance of mice to Banzi
viral infection. The results of this initial study showed that resistance to
infection was 7-fold more sensitive for detection of the IFN response than was ISG54
mRNA and 70-fold more sensitive than either IFN-beta
mRNA or IFN production in serum. In comparison, mouse cells in vitro treated with
poly I:CLC were 3-10-fold less sensitive to its
antiviral action than is the mouse. The results demonstrate that in the four tests in mice, the most sensitive
indicator of
poly I:CLC induction of the IFN system was protection against Banzi
viral infection, followed by ISG54
mRNA levels, IFN-beta
mRNA, and IFN
protein levels. It is hypothesized that the highest sensitivity of mouse protection may be due to priming by the initial
poly I:CLC-induced IFN of the subsequent Banzi virus-induced IFN, resulting in rapid and high concentrations of IFN at the local site of viral replication. Future studies are needed to study other molecular components of the IFN system to identify those that cause the unanticipated high sensitivity of mice to protection against Banzi virus.