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Updated: Nov 3, 2025

Author Spotlight: Improved Method for Production and Purification of Adeno-Associated Viral Vectors
Published on: April 5, 2024
Herpes simplex virus co-infection facilitates rolling circle replication of the adeno-associated virus genome
Anita Felicitas Meier1, Kurt Tobler1, Remo Leisi2
1Institute of Virology, University of Zurich, Zurich, Switzerland.
Abstract:
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.
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