Genomic studies of adeno-associated virus hepatitis

Abstract

In 2022, over 1,000 cases of unexplained paediatric hepatitis in children were reported worldwide, including 278 cases in the UK. Using a combination of genomic, transcriptomic, proteomic, and immunohistochemical methods, we detected high levels of adeno-associated virus 2 (AAV2) DNA in case livers, together with low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B). Nanopore sequencing of liver samples showed alternating and head-to-tail AAV2 concatemers, which are consistent with both HAdV and human herpesvirus-mediated rolling hairpin and rolling circle mediated replication, respectively. 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.

Biography

Dr. Torres Montaguth is a Research Fellow at UCL Great Ormond Street Institute of Child Health, working on clinical metagenomics and viral genomics. He received his PhD in Bioscience Engineering from KU Leuven, Belgium in 2018 working on the characterisation of bacterial defence systems. In 2019, Oscar Enrique joined the Protein-DNA interactions unit at the University of Bristol. His research focuses on the development of Oxford Nanopore technology approaches for the study and characterisation of prokaryotic endonucleases and methyltransferases.