PLA2G16 represents a switch between entry and clearance of Picornaviridae
NATURE
Authors: Staring, Jacqueline; von Castelmur, Eleonore; Blomen, Vincent A.; van den Hengel, Lisa G.; Brockmann, Markus; Baggen, Jim; Thibaut, Hendrik Jan; Nieuwenhuis, Joppe; Janssen, Hans; van Kuppeveld, Frank J. M.; Perrakis, Anastassis; Carette, Jan E.; Brummelkamp, Thijn R.
Abstract
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(1). Although a range of different cell-surface receptors are bound by different picornaviruses(2-7), 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 8-11) 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 Delta PLA2G16 phenotype and identified a mechanism previously implicated in the clearance of intracellular bacteria(12). 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.
Short communication: Inflammation, migration, and cell-cell interaction-related gene network expression in leukocytes is enhanced in Simmental compared with Holstein dairy cows after calving
JOURNAL OF DAIRY SCIENCE
Authors: Lopreiato, V; Minuti, A.; Morittu, V. M.; Britti, D.; Piccioli-Cappelli, F.; Loor, J. J.; Trevisi, E.
Abstract
The aim of this study was to investigate changes in the abundance of genes involved in leukocyte function between cows highly specialized for milk production (Holstein, n = 12) and cows selected for meat and milk (Simmental, n = 13). Blood was collected on d 3 after calving in PAXgene tubes (Preanalytix, Hombrechtikon, Switzerland) to measure mRNA abundance of 33 gens. Normalized gene abundance data were subjected to MIXED model ANOVA using SAS (SAS Institute Inc. Cary, NC). Simmental cows had greater transcript abundance of proinflammatory cytokines and receptor genes (IL1B, TNF, IL1R, TNFRSF1A), cell migration- and adhesion-related genes (CX9CR1, ITGB2, CD44, LGALS8), and the antimicrobial IDO1 gene. In contrast, compared with Holstein cows, Simmental cows had lower abundance of the toll-like receptor (TLR) recognition-related gene TLR2, the antimicrobial-related gene LTF, and S100A8, which is involved in cell maturation, regulation of inflammatory processes, and immune response. These results revealed that breed plays an important role in the modulation of genes involved in immune adaptation and inflammatory response, and the immune system of Simmental cows could potentially have a more acute response in early lactation. In turn, this might be beneficial for mounting a more efficient response after calving and allow for a smoother homeorhetic adaptation to lactation.