[Abstract unavailable

Viruses such as coxsackievirus B3 (CVB3) are entirely host cell-dependent parasites. Indeed, they must cleverly exploit various compartments of host cells to complete their life cycle, and consequently launch disease. Evolution has equipped this pico-rna-virus, CVB3, to use different strategies, including CVB3-induced direct damage to host cells followed by a host inflammatory response to CVB3 infection, and cell death to super-additively promote target organ tissue injury, and dysfunction. In this update, the patho-stratagems of CVB3 are explored from molecular, and systems-level approaches. In summarizing recent developments in this field, we focus particularly on mechanisms by which CVB3 can harness different host cell processes including kinases, host cell-killing and cell-eating machineries, matrix metalloproteinases and miRNAs to promote disease.

Picornaviruses have evolved to hijack host cellular machinery, including the autophagic pathway. However, the mechanisms remain largely unclear. We use coxsackievirus B3 (CVB3) as a model organism to explore the possible role of picornavirus subversion of the autophagic pathway in viral infection. Our in vivo and in vitro experiments demonstrate that CVB3 infection causes a significant, albeit incomplete, inhibition of autophagic flux by limiting the fusion of autophagosomes with lysosomes and/or late endosomes. Furthermore, we show that CVB3 specifically targets SNARE protein SNAP29 and adaptor protein PLEKHM1, two critical proteins known to regulate autophagosome fusion, for cleavage through the catalytic activity of viral proteinase 3C, ultimately impairing the formation of SNARE complexes. Finally, we demonstrate that loss of SNAP29/PLEKHM1 inhibits autophagic flux, resulting in increased viral replication. Collectively, our study reveals a mechanism that supports an emerging model whereby CVB3 hijacks the autophagic machinery to facilitate its own propagation.