RESUMEN
Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah-/- mice, lethal influenza infection led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation. This was underpinned by differential lipid droplet dynamics as well as reduced viral replication and virus-induced inflammation in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza replication in macrophages and their inflammatory potential. Our findings define how the expression of OLAH drives life-threatening viral disease.
Asunto(s)
COVID-19 , Gripe Humana , Animales , Humanos , Ratones , COVID-19/virología , COVID-19/genética , Gripe Humana/virología , Replicación Viral , Macrófagos/metabolismo , Macrófagos/virología , Femenino , Masculino , SARS-CoV-2 , Pulmón/virología , Pulmón/patología , Pulmón/metabolismo , Ratones Endogámicos C57BL , Ácido Oléico/metabolismo , Infecciones por Virus Sincitial Respiratorio/virología , Ratones Noqueados , Carga Viral , Hidrolasas de Éster Carboxílico/metabolismo , Hidrolasas de Éster Carboxílico/genética , Infecciones por Orthomyxoviridae/virología , Infecciones del Sistema Respiratorio/virología , NiñoRESUMEN
Meat inspection (MI) is essential to verify compliance with legal requirements related to human and animal health and animal welfare protections. Judgement criteria applied during MI, resulting in condemnation data of importance, among other things, for livestock producers and for benchmarking reasons. However, although the Meat Inspection Regulation sets out judgement criteria, most are generic, favouring flexibility, but also subjectivity. To address the degree of variation on total condemnation (TC) criteria applied during post-mortem inspection (PMI) of finishing pigs, an online survey was prepared aiming to collect this information from several European countries. The focus was on TC criteria regarding the following PMI findings: abscesses, arthritis, cachexia, erysipelas, icterus, Mycobacterium-like lesions, osteomyelitis, peritonitis, pleuritis and pneumonia. From September to November 2020, a total of 44 completed questionnaires were obtained from 26 European countries. The results showed a substantial variation in the TC criteria in place in the participating countries. One of the main reasons for the variability seen in the respondents' reported answers was related to the indicators used to define a generalised condition related to the 10 PMI findings addressed, making harmonisation a challenge and avoiding to draw conclusions when comparing condemnation causes between abattoirs. This implies that it would make sense to look into how a generalised condition can be identified/described and how it should be judged. The results should be used as inspiration towards possible harmonisation, improving decision-making, and permitting comparative analysis between different reports to allow trend analyses and benchmarking.