Oscar Enrique Torres Montaguth from the University College London in the UK presented a short talk at London Calling. The title was “Genomic studies of adeno-associated virus hepatitis.” They studied the 2022 pediatric hepatitis outbreak using metagenomic sequencing approaches. They identified AAV2 in liver and blood samples of almost all cases, and adenoviruses and herpesviruses were also possibly involved. The team hypothesized that it was an immune-related response caused by viruses. AAVs are commonly used as vectors in gene therapy. Hepatitis is a common side effect of this treatment thought to be caused by an innate and adaptive immune response to the vector. There are similarities between the two forms of hepatitis. The research team studied viral vectors and used short and long-read sequencing to sequence samples from controls and hepatitis patients. There was evidence of all three plasmids in liver biopsy samples. The outbreak samples had complex AAV DNA in liver. Montaguth concluded that there are similarities between the 2022 outbreak of pediatric hepatitis and hepatitis following AAV gene therapy. The evidence of viral proteins is emerging. The use of sequencing to identify viral sequences is helping find support for co-infection and immune responses.
