The question of whether
interferon alpha/beta is the common mechanism of
antiviral action of synthetic
immunomodulators was investigated in B6C3F1 mice infected with Semliki Forest virus. Mice were treated with various concentrations of normal sheep serum or potent anti-alpha/
beta interferon antiserum, inoculated with the
immunomodulators, and infected 24 hours later with virus. Three patterns emerged. The
antiviral action of the
pyrimidinone (ABMP) and the oral
interferon inducer (CL246,738) appeared to be mediated primarily by
interferon alpha/beta; their protective ability was almost completely abrogated by treatment with low levels of anti-alpha/
beta interferon antiserum. The
antiviral action of two other
immunomodulators, a mismatched polyribonucleotide (
Ampligen) and a polyanionic copolymer (MVE-2) at least partially involved
interferon. Activity of these compounds was reduced, but not consistently eliminated by treatments with high doses of antiserum. The
antiviral activity of another polyribonucleotide, polyriboinosinic-
cytidylic acid complexed with
lysine carboxymethylcellulose (
poly ICLC), was not affected by treatment with even the highest amount of antiserum (two
injections of 100,000 neutralizing units each). Almost complete protection by
poly ICLC was observed despite the fact that this high concentration of antiserum, when given alone, caused a decrease in natural resistance to
Semliki Forest virus infection. Taken together, these results indicate that induction of
interferon alpha/beta does not appear to be the major common mechanism of
antiviral activity among these diverse synthetic
immunomodulators.