Herpes simplex virus co-infection facilitates rolling circle replication of the adeno-associated virus genome.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
06 2021
Historique:
received: 04 03 2021
accepted: 13 05 2021
revised: 11 06 2021
pubmed: 2 6 2021
medline: 8 10 2021
entrez: 1 6 2021
Statut: epublish

Résumé

Adeno-associated virus (AAV) genome replication only occurs in the presence of a co-infecting helper virus such as adenovirus type 5 (AdV5) or herpes simplex virus type 1 (HSV-1). AdV5-supported replication of the AAV genome has been described to occur in a strand-displacement rolling hairpin replication (RHR) mechanism initiated at the AAV 3' inverted terminal repeat (ITR) end. It has been assumed that the same mechanism applies to HSV-1-supported AAV genome replication. Using Southern analysis and nanopore sequencing as a novel, high-throughput approach to study viral genome replication we demonstrate the formation of double-stranded head-to-tail concatemers of AAV genomes in the presence of HSV-1, thus providing evidence for an unequivocal rolling circle replication (RCR) mechanism. This stands in contrast to the textbook model of AAV genome replication when HSV-1 is the helper virus.

Identifiants

pubmed: 34061891
doi: 10.1371/journal.ppat.1009638
pii: PPATHOGENS-D-21-00480
pmc: PMC8195378
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1009638

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Anita Felicitas Meier (AF)

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

Kurt Tobler (K)

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

Remo Leisi (R)

Department for Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.

Anouk Lkharrazi (A)

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

Carlos Ros (C)

Department for Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.

Cornel Fraefel (C)

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

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