Expression of interferon dependent resistance to influenza virus in mouse embryo cells

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Abstract
Adult but not newborn mice bearing the alleleMx display a specific resistance toin vivo infection with orthomyxoviruses.In vitro, cells isolated from adultMx-animals exhibit a several hundred-fold higher sensitivity to the action of interferon (IFN) against influenza viruses than do cells fromMx-negative mice. We here tested whether or not cells from immatureMx-bearing animals would likewise express the virus-specific higher sensitivity to IFN. Cultured cells from 16-day gestation mouse embryos with and withoutMx were equally permissive for an influenza virus when single cycle virus growth was measured. However, influenza virus plaques were smaller inMx-cells. Treatment of cells with mouse interferon reduced viral protein synthesis, single cycle virus yields and the number of virus plaques more efficiently inMx-cells than in non-Mx-cells. The smaller size of influenza virus plaques inMx-cells not treated with IFN seems to be due to the action of endogenous IFN: inclusion of anti-interferon antibodies in the agar overlay during plaque formation resulted in plaques of approximately the size seen in control cells. When treated with the same dose of IFN, cells withMx developed protection against influenza virus more rapidly than cells withoutMx. However, after removal of IFN, the antiviral protection decayed more rapidly in cells withoutMx. No differences in sensitivity to IFN, viral plaque formation and kinetics of induction and decay of the antiviral state were observed between the two cell types when the rhabdovirus VSV was used as challenge. Thus, the alleleMx is expressed in cultured embryo cells much as in cells from adult animals, and susceptibility of newbornMx-animals to influenza virus infection cannot be due to inability of their cells to respond to IFN appropriately.

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