Why the study?
Complete kinetic models are pervasive in chemistry but lacking in biological systems.
Modeling the complete kinetics of CVB3 infection provides insights into viral-host interactions and reveals how a common human MAVS polymorphism can elevate viral infectivity.
Complete CVB3 kinetic model enables systems analysis of viral myocarditis pathogenesis; leaves open clinical validation and therapeutic application.
SUMMARY Complete 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 fast-acting 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.
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Lopacinski et al. (2020) studied this question.
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