Author: ["Jacqueline Staring","Eleonore von Castelmur","Vincent A. Blomen","Lisa G. van den Hengel","Markus Brockmann","Jim Baggen","Hendrik Jan Thibaut","Joppe Nieuwenhuis","Hans Janssen","Frank J. M. van Kuppeveld","Anastassis Perrakis","Jan E. Carette","Thijn R. Brummelkamp"]
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Abstract
The phospholipase PLA2G16 is required for the entry of picornaviruses, and in its absence, virus infection is prevented by a galectin-8-mediated process. Thijn Brummelkamp and colleagues use a genome-wide haploid genetic screen to identify the host factors required for the replication of picornaviruses. They identify the small phospholipase PLA2G16 as being required for the cytoplasmic delivery of the viral genome. In a second screen to find mutants that restored virus susceptibility to PLA2G16-deficient cells, the authors identify galectin-8, a sensor previously implicated in the autophagic clearance of intracellular bacteria. The precise function of PLA2G16 remains unclear, but the authors suggest that it facilitates the displacement of the viral genome from galactin-8-positive vesicles. Picornaviruses are a leading cause of human and veterinary infections that result in various diseases, including polio and the common cold. As archetypical non-enveloped viruses, their biology has been extensively studied1. Although a range of different cell-surface receptors are bound by different picornaviruses2,3,4,5,6,7, it is unclear whether common host factors are needed for them to reach the cytoplasm. Using genome-wide haploid genetic screens, here we identify the lipid-modifying enzyme PLA2G16 (refs 8, 9, 10, 11) as a picornavirus host factor that is required for a previously unknown event in the viral life cycle. We find that PLA2G16 functions early during infection, enabling virion-mediated genome delivery into the cytoplasm, but not in any virion-assigned step, such as cell binding, endosomal trafficking or pore formation. To resolve this paradox, we screened for suppressors of the ΔPLA2G16 phenotype and identified a mechanism previously implicated in the clearance of intracellular bacteria12. The sensor of this mechanism, galectin-8 (encoded by LGALS8), detects permeated endosomes and marks them for autophagic degradation, whereas PLA2G16 facilitates viral genome translocation and prevents clearance. This study uncovers two competing processes triggered by virus entry: activation of a pore-activated clearance pathway and recruitment of a phospholipase to enable genome release.Cite this article
Staring, J., von Castelmur, E., Blomen, V. et al. PLA2G16 represents a switch between entry and clearance of Picornaviridae. Nature 541, 412–416 (2017). https://doi.org/10.1038/nature21032 