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Experimental studies of the innate immune response of mammalian cells to viruses reveal pervasive heterogeneity at the level of single cells. Interferons are induced only in a fraction of virus-infected cells; subsequently a fraction of cells exposed to interferons upregulate interferon-stimulated genes. Nevertheless, quantitative experiments and linked mathematical models show that the interferon response can be effective in curbing viral spread through two distinct mechanisms. First, paracrine interferon signals from scattered source cells can protect many uninfected cells, and the self-amplification of interferon production might serve to calibrate response amplitude to strength of viral infection. Second, models of the tug-of-war between viral replication and the innate interferon response imply a pivotal role of interferon action on already infected cells in curbing viral spread, through effectively lowering virus replication rate. This finding is in line with the observation that several pathogenic viruses selectively abrogate interferon action on infected cells. Thus, interferons may delay viral spread in acute infections by acting as sentinels, warning uninfected cells of imminent danger, or as negative feedback regulators of virus replication in infected cells. The timing of the interferon response relative to the onset of viral replication is critical for its effectiveness in curbing viral spread.

Arsenic has a dual role as causative and curative agent of human disease. Therefore, there is considerable interest in elucidating arsenic toxicity and detoxification mechanisms. By an ensemble modelling approach, we identified a best parsimonious mathematical model which recapitulates and predicts intracellular arsenic dynamics for different conditions and mutants, thereby providing novel insights into arsenic toxicity and detoxification mechanisms in yeast, which could partly be confirmed experimentally by dedicated experiments. Specifically, our analyses suggest that: (i) arsenic is mainly protein-bound during short-term (acute) exposure, whereas glutathione-conjugated arsenic dominates during long-term (chronic) exposure, (ii) arsenic is not stably retained, but can leave the vacuole via an export mechanism, and (iii) Fps1 is controlled by Hog1-dependent and Hog1-independent mechanisms during arsenite stress. Our results challenge glutathione depletion as a key mechanism for arsenic toxicity and instead suggest that (iv) increased glutathione biosynthesis protects the proteome against the damaging effects of arsenic and that (v) widespread protein inactivation contributes to the toxicity of this metalloid. Our work in yeast may prove useful to elucidate similar mechanisms in higher eukaryotes and have implications for the use of arsenic in medical therapy.