Adeno-associated virus 2 capsid. Image source: LAGUNA DESIGN/SCIENCE PHOTO LIBRARY
Two independent studies in the UK in children with unexplained liver injury or hepatitis found that almost all affected children had a virus called adeno-associated virus 2, which was not found in other children, and almost all children with hepatitis developed a genetic variant that affected their immune response.
Adeno-associated virus 2 (AAV2) is a common virus that infects almost everyone in early childhood, but it was previously thought that it would not cause any disease. The virus can integrate its own DNA into the genome of infected cells, leaving it in the body indefinitely.
However, AAV2 is rather unusual, and it can only replicate in the presence of other viruses, such as adenovirus or herpes viruses. Emma Thomson of the University of Glasgow in the United Kingdom believes that it is unclear whether AAV2 is the cause of hepatitis or just an indicator of adenovirus infection.
These findings suggest that AAV2 or other viruses may trigger liver damage in children with a genetic predisposition through an unknown immune mechanism. “Virus-induced hepatitis may have immune-mediated causes, and we need more work to test this hypothesis.” Thomson said.
She suspects that a small percentage of cases in the study have not been found to be infected with an adenovirus for years. In Scotland, the number of adenovirus infections is lower than usual due to COVID-19 prevention and control measures, and if the measures are relaxed, adenovirus infections will reach a peak, which may lead to many cases of hepatitis occurring simultaneously.
In April, Scotland reported a group of cases of liver injury in children that were not caused by the usual hepatitis virus, and the children initially had gastrointestinal symptoms such as diarrhea and developed hepatitis in the following weeks.
To find out the cause, Thomson’s team studied nine children with hepatitis, 12 healthy children of the same age, and 13 children infected with adenovirus without liver damage, sequencing all the DNA and RNA in their blood samples. It was found that AAV2 was found in all 9 children with hepatitis, but not in other children. Liver samples were available in 4 of the 9 children and AAV2 was present in the livers of all 4 children.
The team also found that eight out of nine children carried a variant of the gene called HLA-DRB1*04:01, which can affect the immune system’s response to infection. In Scotland, only 16% of people have this variant.
A team led by Judith Breuer, a team at University College London’s Great Ormond Street Institute for Child Health, did a similar study, comparing blood samples from 28 children with hepatitis and another 136 children. The results found that 27 of the 28 children had AAV2 in their blood, and other children’s blood samples had no AAV2 or only very low levels of AAV2.
Breuer’s team also found AAV2 RNA in 5 liver samples, but could not find viral proteins or see viral particles under electron microscopy. This, he argues, suggests the existence of an indirect viral mechanism that requires international collaboration to conduct larger-scale studies to confirm these findings and to try to identify potential mechanisms. (Source: China Science Daily Xin Yu)
Related paper information:https://doi.org/10.1101/2022.07.19.22277425