Open AccessHerpes simplex virus co-infection facilitates rolling circle replication of the adeno-associated virus genome
Author(s) -
Anita F. Meier,
Kurt Tobler,
Remo Leisi,
Anouk Lkharrazi,
Carlos Ros,
Cornel Fraefel
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009638
Subject(s) - genome , virology , biology , herpes simplex virus , viral replication , helper virus , virus , rolling circle replication , origin of replication , adeno associated virus , concatemer , dna replication , genetics , gene , vector (molecular biology) , recombinant dna
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.