Herpes Simplex Virus 1 Coinfection Modifies Adeno-associated Virus Genome End Recombination.


Journal

Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724

Informations de publication

Date de publication:
10 06 2021
Historique:
pubmed: 16 4 2021
medline: 26 8 2021
entrez: 15 4 2021
Statut: ppublish

Résumé

Wild-type adeno-associated virus (AAV) can only replicate in the presence of helper factors, which can be provided by coinfecting helper viruses such as adenoviruses and herpesviruses. The AAV genome consists of a linear, single-stranded DNA (ssDNA), which is converted into different molecular structures within the host cell. Using high-throughput sequencing, we found that herpes simplex virus 1 (HSV-1) coinfection leads to a shift in the type of AAV genome end recombination. In particular, open-end inverted terminal repeat (ITR) recombination was enhanced, whereas open-closed ITR recombination was reduced in the presence of HSV-1. We demonstrate that the HSV-1 protein ICP8 plays an essential role in HSV-1-mediated interference with AAV genome end recombination, indicating that the previously described ICP8-driven mechanism of HSV-1 genome recombination may be underlying the observed changes. We also provide evidence that additional factors, such as products of true late genes, are involved. Although HSV-1 coinfection significantly changed the type of AAV genome end recombination, no significant change in the amount of circular AAV genomes was identified.

Identifiants

pubmed: 33853961
pii: JVI.00486-21
doi: 10.1128/JVI.00486-21
pmc: PMC8315985
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0048621

Subventions

Organisme : Medical Research Council
ID : MR/N022890/1
Pays : United Kingdom
Organisme : Swiss National Science Foundation
ID : P1ZHP3_174912
Pays : Switzerland
Organisme : Swiss National Science Foundation
ID : 310030_184766/1
Pays : Switzerland
Organisme : UKRI | Medical Research Council (MRC)
ID : MR/N022890/1

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Auteurs

Anita Felicitas Meier (AF)

Institute of Virology, University of Zürich, Zurich, Switzerland.

Kurt Tobler (K)

Institute of Virology, University of Zürich, Zurich, Switzerland.

Kevin Michaelsen (K)

Institute of Virology, University of Zürich, Zurich, Switzerland.

Bernd Vogt (B)

Institute of Virology, University of Zürich, Zurich, Switzerland.

Els Henckaerts (E)

Laboratory of Viral Cell Biology & Therapeutics, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.
Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.

Cornel Fraefel (C)

Institute of Virology, University of Zürich, Zurich, Switzerland.

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Classifications MeSH