Project description:Since the first reports of hepatitis of unknown aetiology occurring in UK children, over 1000 cases have been reported worldwide, including 268 cases in the UK, with the majority younger than 6 years old. Using genomic, proteomic and immunohistochemical methods, we undertook extensive investigation of 28 cases and 136 control subjects. In five cases who underwent liver transplantation, we detected high levels of adeno-associated virus 2 (AAV2) in the explanted livers. AAV2 was also detected at high levels in blood from 10/11 non-transplanted cases. Low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), both of which enable AAV2 lytic replication, were also found in the five explanted livers and blood from 15/17 and 6/9 respectively, of the 23 non-transplant cases tested. In contrast, AAV2 was detected at low titre in 6/100 whole bloods from child controls from cohorts with presence or absence of hepatitis and/or adenovirus infection. Our data show an association of AAV2 at high titre in blood or liver tissue, with unexplained hepatitis in children infected in the recent HAdV-F41 outbreak. We were unable to find evidence by electron microscopy, immunohistochemistry or proteomics of HAdV or AAV2 viral particles or proteins in explanted livers, suggesting that hepatic pathology is not due to direct lytic infection by either virus. The potential that AAV2, although not previously associated with disease, may, together with HAdV-F41 and/or HHV-6, be causally implicated in the outbreak of unexplained hepatitis, requires further investigation.
Project description:A food-borne outbreak of haemorrhagic colitis (HC) and HUS caused by E. coli O103:H25 occurred in Norway, 2006. The outbreak included 17 registered cases, of which 10 developed HUS. The aim of this study was to characterize two E. coli O103:H25 isolates from this outbreak. Only one of the isolates carry the stx2 gene (by PCR). Since they have the same typing profile by typing method MLVA, we expect the isolates to have identical gene content except from an Stx2-encoding phage. Therefore, we further investigate whether the Stx2-encoding phage has any impact on the gene expression. Keywords: mixed, gene expression, comparative genomic hybridization
Project description:A food-borne outbreak of haemorrhagic colitis (HC) and HUS caused by E. coli O103:H25 occurred in Norway, 2006. The outbreak included 17 registered cases, of which 10 developed HUS. The aim of this study was to characterize two E. coli O103:H25 isolates from this outbreak. Only one of the isolates carry the stx2 gene (by PCR). Since they have the same typing profile by typing method MLVA, we expect the isolates to have identical gene content except from an Stx2-encoding phage. Therefore, we further investigate whether the Stx2-encoding phage has any impact on the gene expression. Keywords: mixed, gene expression, comparative genomic hybridization Triplicate samples of mRNA from a test strain O157:H7 EDL933 and two outbreak strains - one Stx positive and one stx negative were co-hybridized with genomic DNA from the same strain. Triplicate samples of the Stx positive strain grown at acidic conditions was also co-hybridized with genomic DNA from the Stx positive strain. Genomic DNA for each strain is technical replicates only.