Mouse genes influence antiviral action of interferon in vivo

BALB/c mice are more sensitive to the antiviral effect of interferon than C57BL/6 mice, as demonstrated by experiments involving protection against lethal infection with encephalomyocarditis virus. This greater sensitivity of the BALB/c genotype to interferon action is in accord with previous observations that the bone marrow-derived erythroid precursors and macrophages of BALB/c mice are more sensitive to the anti-proliferative action of interferon than those of C57BL/6 mice. An analysis of the loci involved in the modulation of the activity of interferon against encephalomyocarditis virus infection was carried out in (BALB/c x C57BL/6)F1 progeny and in six recombinant inbred lines originally derived from a BALB/c x C57BL/6 cross. The antiviral effect of exogenous interferon in the F1 progeny was comparable to the effect in BALB/c mice, indicating dominance of the greater sensitivity to interferon action. The results obtained with the six recombinant inbred lines suggested a multifactorial influence. In vitro, interferon pretreatment of encephalomyocarditis virus-infected BALB/c and C57BL/6 fibroblast cultures did not reveal a difference in sensitivity between the two mouse genotypes. This finding demonstrates that it is not always possible to extrapolate from in vitro to in vivo when sensitivity to interferon action is studied.