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PLA2G16 represents a switch between entry and clearance of Picornaviridae

Staring, Jacqueline (author)
Netherlands Cancer Institute, Amsterdam, The Netherlands
von Castelmur, Eleonore (author)
Netherlands Cancer Institute, Amsterdam, The Netherlands
Blomen, Vincent A (author)
Netherlands Cancer Institute, Amsterdam, The Netherlands
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van den Hengel, Lisa G (author)
Netherlands Cancer Institute, Amsterdam, The Netherlands
Brockmann, Markus (author)
Netherlands Cancer Institute, Amsterdam, The Netherlands
Baggen, Jim (author)
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
Thibaut, Hendrik Jan (author)
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
Nieuwenhuis, Joppe (author)
Netherlands Cancer Institute, Amsterdam, The Netherlands
Janssen, Hans (author)
Netherlands Cancer Institute, Amsterdam, The Netherlands
van Kuppeveld, Frank J M (author)
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
Perrakis, Anastassis (author)
Netherlands Cancer Institute, Amsterdam, The Netherlands
Carette, Jan E (author)
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA
Brummelkamp, Thijn R (author)
Netherlands Cancer Institute, Amsterdam, The Netherlands; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria; Cancer GenomiCs.nl (CGC.nl), Amsterdam, The Netherlands
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 (creator_code:org_t)
2017-01-11
2017
English.
In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 541:7637, s. 412-416
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  • Journal article (peer-reviewed)
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  • 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 studied. Although a range of different cell-surface receptors are bound by different picornaviruses, 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 bacteria. 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.

Subject headings

NATURVETENSKAP  -- Kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

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