Modeling the complete kinetics of coxsackievirus B3 reveals human determinants of host-cell feedback Graphical abstract Highlights d A complete kinetic model of acute infection by the coxsackievirus B3 enterovirus d Enteroviral replication organelles accelerate biochemistry on membrane surfaces d Type I interferon exaggerates different enteroviral susceptibilities of host cells d A common polymorphism in MAVS alters host-cell susceptibility to coxsackievirus B3

Using phototaxis as a behavioral measure of photosensitivity, the spectral sensitivity ofSagitta hispida Conant (Chaetognatha) was determined. S. hispida is most sensitive to blue-green light, with maximum sensitivity at 500 nm. From 400-580 nm, the shape of the action spectrum for phototaxis approximates an absorbance spectrum for a rhodspin-based visual pigment. This suggests that photoreception is mediated largely by a single major pigment. An accessory pigment may play a role in photoreception at longer wavelengths. S. hispida is adapted for greatest photosensitivity wherever blue-green light dominates the available spectrum. This finding is consistent with the geographical range of this species, which comprises relatively clear bluegreen tropical and subtropical seas.

In estuarine waters at Beaufort, North Carolina, adult Sagitta hispida perform a diel vertical migration. By day, few adult chaetognaths are found in the 7 m water column. Shortly after sunset their numbers increase rapidly at all depths. We hypothesized that the evening ascent is dependent on photoresponses elicited by some aspect of the change in light intensity occurring at sunset. In the laboratory, S. hispidaû pswimming increases markedly whenever light intensity drops below 10 167 photons m~ 2 s~'. Animals adapted to light intensities below this level, and to darkness, show strong upswimming. This indicates that continuously decreasing light intensity is not required to maintain the upswimming response. In the field, in the afternoon and evening, downward irradiance values of 10 167 photons m 2 -s~' are found only at sunset. These findings suggest that the daily ascent of 5. hispida occurs as an all-ornone phenomenon, dependent only on exposure to light intensities below approximately 10 167 photons m" 2 -s~'. This threshold intensity for ascent lies above the threshold for photoreception in this species, suggesting that the ascent begins as a positive phototaxis. However, experiments in which light direction was reversed indicated that the ascent is geotactic or photokinetic, since changes in light direction had little bearing on the orientation of the upswimming response.

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SUMMARYComplete kinetic models are pervasive in chemistry but lacking in biological systems. We encoded the complete kinetics of infection for coxsackievirus B3 (CVB3), a compact and fastacting RNA virus. The kinetics are built from detailed modules for viral binding–delivery, translation–replication, and encapsidation. Specific module activities are dampened by the type I interferon response to viral double-stranded RNAs (dsRNAs), which is itself disrupted by viral proteinases. The validated kinetics uncovered that cleavability of the dsRNA transducer mitochondrial antiviral signaling protein (MAVS) becomes a stronger determinant of viral outcomes when cells receive supplemental interferon after infection. Cleavability is naturally altered in humans by a common MAVS polymorphism, which removes a proteinase-targeted site but paradoxically elevates CVB3 infectivity. These observations are reconciled with a simple nonlinear model of MAVS regulation. Modeling complete kinetics is an attainable goal for small, rapidly infecting viruses and perhaps viral pathogens more broadly.