Postpandemic rebound of adeno‐associated virus type 2 (AAV2) infections temporally associated with an outbreak of unexplained severe acute hepatitis in children in the United Kingdom

Gates, S.; Andréani, Julien; Dewar, Rebecca; Smith, Donald B.; Templeton, Kate; Child, Harry T; Breuer, Judith; Golubchik, Tanya; Bassano, Irene; Wade, Matthew J.; Jeffries, Aaron R.; Simmonds, Peter; Harvala, Heli

doi:10.1002/jmv.28921

Cited by 7 publications

(2 citation statements)

References 32 publications

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“…Given that community lockdowns may have altered children’s regular exposure patterns and immunity, those with a specific genetic background may have been more susceptible to viral coinfections [ 30 , 31 ]. Of note, three months after the publication of the Nature studies, Gates and colleagues (2023) [ 32 ] investigated the epidemiology of AAV in the United Kingdom by analyzing 300 pediatric respiratory samples collected before (April 2009–April 2013) and during (April 2022) the COVID-19 pandemic. Wastewater samples were also collected from 50 locations in London (August 2021–March 2022).…”

Section: Main Textmentioning

confidence: 99%

A dual role for adeno-associated virus in human health

Araujo

2023

Virol J

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Adeno-associated virus (AAV) differs from most other viruses, as it requires the simultaneous presence of a helper virus for an active infection. Up to 80% of the human population is seropositive for AAV antibodies. AAV has been known to be a non-pathogenic virus and an inhibitor of carcinogenesis caused by coinfecting viruses. However, the recent reports associating AAV infection with hepatocellular carcinoma development and the mysterious cases of acute severe hepatitis in children have challenged the idea that AAV is a harmless virus. Herein, we explore the usefulness of AAV in gene therapy and the importance of AAV as a protector or perpetrator in human carcinogenesis, ultimately reflecting on the dual role of AAV in human health.

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Section: Main Textmentioning

confidence: 99%

A dual role for adeno-associated virus in human health

Araujo

2023

Virol J

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“…At this time the early non‐A to E hepatitis cases were observed; the epidemic peaked in April 2022 when also a broad peak of SARS‐CoV‐2 infections was observed following the relaxation of the distancing restrictions on 24 February 2022 in England. In clinical samples, HAdV and AAV2 detection was significantly correlated and peak AAV2 detection was seen in 2‐year‐old children (Gates et al, 2023 ).…”

Section: Supporting Evidence: Wastewater Studiesmentioning

confidence: 99%

Non‐A to E hepatitis in children: Detecting a novel viral epidemic during the COVID‐19 pandemic

Brüssow

2023

Microbial Biotechnology

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During the COVID‐19 pandemic, two further novel viral epidemics were described in 2022, monkeypox virus infections in men having sex with men and non‐A to E hepatitis in children. The latter occurred in the first half of 2022 with about 1000 cases worldwide, necessitating liver transplantation in 5% and causing death in 2% of patients. It took some effort to clarify the cause of the novel hepatitis epidemic. Researchers were confronted with a polymicrobial viral infection consisting of an adenovirus‐associated virus type 2 (AAV2) infection, co‐occurring with either human adenovirus type 41 (HAdV41) or herpesvirus infections; most prominently human herpesvirus type 6 (HHV‐6). AAV‐2, a small Dependovirus of the Parvovirus family, needs these helper viruses for its replication. AAV2 is used as a vector for liver‐targeting gene therapy but was not previously known to cause acute hepatitis. HAdV41 and HHV‐6 are mostly known to cause diarrhoea and febrile illnesses associated with skin rashes in children, respectively. Except for a few case reports of HHV‐6 hepatitis, HAdV and HHV‐6 are mostly known as major pathogens in immunosuppressed transplantation patients. A potential role of SARS‐CoV‐2 has also been discussed but the most popular hypothesis involves an indirect role of the COVID‐19 pandemic for this novel disease. Exposure to HHV‐6 infections occurs nearly quantitatively during the first year of life. Social distancing measures, followed by the lifting of these measures in 2022 might have caused a delayed exposure to multiple, normally benign childhood viral infections eliciting a dysregulated immune response with pathological effects for liver cells. In the fall of 2022, when these conditions were not longer met, case numbers dwindled. The hypothesis of an unequilibrated immune response instead of intrinsic cytopathic activity of the implicated viruses is further supported by the enrichment of a particular HLA allele in cases over controls.

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AAV‐mediated Gene Therapy for Hereditary Deafness: Progress and Perspectives

Zhang,

Tan,

et al. 2024

Advanced Science

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Hereditary deafness is the most prevalent sensory deficit disorder, with over 100 identified deafness‐related genes. Clinical treatment options are currently limited to external devices like hearing aids and cochlear implants. Gene therapy has shown promising results in various genetic disorders and has emerged as a potential treatment for hereditary deafness. It has successfully restored hearing function in >20 types of genetic deafness model mice and can almost completely cure patients with hereditary autosomal recessvie deafness 9 (DFNB9) caused by the OTOFERLIN (OTOF) mutation, thus serving as a translational paradigm for gene therapy for other forms of genetic deafness. However, due to the complexity of the inner ear structure, the diverse nature of deafness genes, and variations in transduction efficiency among different types of inner ear cells targeted by adeno‐associated virus (AAV), precision gene therapy approaches are required for different genetic forms of deafness. This review provides a comprehensive overview of gene therapy for hereditary deafness, including preclinical studies and recent research advancements in this field as well as challenges associated with AAV‐mediated gene therapy.

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Postpandemic rebound of adeno‐associated virus type 2 (AAV2) infections temporally associated with an outbreak of unexplained severe acute hepatitis in children in the United Kingdom

Cited by 7 publications

References 32 publications

A dual role for adeno-associated virus in human health

A dual role for adeno-associated virus in human health

Non‐A to E hepatitis in children: Detecting a novel viral epidemic during the COVID‐19 pandemic

AAV‐mediated Gene Therapy for Hereditary Deafness: Progress and Perspectives

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