Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1 . Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed.AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells.Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins.HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

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In aquatic environments, plastic pollution occurs concomitantly with anthropogenic climate stressors such as ocean acidification. Within the Southern Ocean, Antarctic krill (Euphausia Superba) support many marine predators and play a key role in the biogeochemical cycle. Ocean acidification and plastic pollution have been acknowledged to hinder Antarctic krill development and physiology in singularity, however potential multi-stressor effects of plastic particulates coupled with ocean acidification are unexplored. Furthermore, Antarctic krill may be especially vulnerable to plastic pollution due to their close association with sea-ice, a known plastic sink. Here, we investigate the behaviour of nanoplastic [spherical, aminated (NH2), and yellow-green fluorescent polystyrene nanoparticles] in Antarctic seawater and explore the single and combined effects of nanoplastic (160 nm radius, at a concentration of 2.5 μg ml–1) and ocean acidification (pCO2 ∼900, pHT 7.7) on the embryonic development of Antarctic krill. Gravid female krill were collected in the Atlantic sector of the Southern Ocean (North Scotia Sea). Produced eggs were incubated at 0.5 °C in four treatments (control, nanoplastic, ocean acidification and the multi-stressor scenario of nanoplastic presence, and ocean acidification) and their embryonic development after 6 days, at the incubation endpoint, was determined. We observed that negatively charged nanoplastic particles suspended in seawater from the Scotia Sea aggregated to sizes exceeding the nanoscale after 24 h (1054.13 ± 53.49 nm). Further, we found that the proportion of embryos developing through the early stages to reach at least the limb bud stage was highest in the control treatment (21.84%) and lowest in the multi-stressor treatment (13.17%). Since the biological thresholds to any stressors can be altered by the presence of additional stressors, we propose that future nanoplastic ecotoxicology studies should consider the changing global ocean under future climate scenarios for assessments of their impact and highlight that determining the behaviour of nanoplastic particles used in incubation studies is critical to determining their toxicity.