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.
Highlights
Adeno-associated virus (AAV) is a small, non-pathogenic Dependoparvovirus and is predominantly known for its application in gene therapy [1,2]
Efficient adeno-associated virus (AAV) replication requires the presence of helper factors, which can be provided by co-infecting helper viruses such as adenoviruses or herpesviruses
This study stands in contrast to the textbook model of AAV genome replication
Summary
Adeno-associated virus (AAV) is a small, non-pathogenic Dependoparvovirus and is predominantly known for its application in gene therapy [1,2]. HSV-1 promotes rolling circle replication of AAV2 DNA study design, data collection and analysis, decision to publish, or preparation of the manuscript
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