PMID- 34061891
OWN - NLM
STAT- MEDLINE
DCOM- 20211007
LR  - 20231111
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 17
IP  - 6
DP  - 2021 Jun
TI  - Herpes simplex virus co-infection facilitates rolling circle replication of the 
      adeno-associated virus genome.
PG  - e1009638
LID - 10.1371/journal.ppat.1009638 [doi]
LID - e1009638
AB  - 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.
FAU - Meier, Anita Felicitas
AU  - Meier AF
AUID- ORCID: 0000-0002-7691-0735
AD  - Institute of Virology, University of Zurich, Zurich, Switzerland.
FAU - Tobler, Kurt
AU  - Tobler K
AUID- ORCID: 0000-0002-0013-7993
AD  - Institute of Virology, University of Zurich, Zurich, Switzerland.
FAU - Leisi, Remo
AU  - Leisi R
AUID- ORCID: 0000-0001-7019-0098
AD  - Department for Chemistry, Biochemistry and Pharmaceutical Sciences, University of 
      Bern, Bern, Switzerland.
FAU - Lkharrazi, Anouk
AU  - Lkharrazi A
AUID- ORCID: 0000-0002-7687-3516
AD  - Institute of Virology, University of Zurich, Zurich, Switzerland.
FAU - Ros, Carlos
AU  - Ros C
AUID- ORCID: 0000-0002-6964-4002
AD  - Department for Chemistry, Biochemistry and Pharmaceutical Sciences, University of 
      Bern, Bern, Switzerland.
FAU - Fraefel, Cornel
AU  - Fraefel C
AUID- ORCID: 0000-0001-7221-6706
AD  - Institute of Virology, University of Zurich, Zurich, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210601
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - *Coinfection
MH  - *Dependovirus
MH  - Genome, Viral
MH  - Helper Viruses/physiology
MH  - Herpes Simplex
MH  - Humans
MH  - Parvoviridae Infections
MH  - *Simplexvirus
MH  - *Virus Replication
PMC - PMC8195378
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/06/02 06:00
MHDA- 2021/10/08 06:00
PMCR- 2021/06/01
CRDT- 2021/06/01 17:24
PHST- 2021/03/04 00:00 [received]
PHST- 2021/05/13 00:00 [accepted]
PHST- 2021/06/11 00:00 [revised]
PHST- 2021/06/02 06:00 [pubmed]
PHST- 2021/10/08 06:00 [medline]
PHST- 2021/06/01 17:24 [entrez]
PHST- 2021/06/01 00:00 [pmc-release]
AID - PPATHOGENS-D-21-00480 [pii]
AID - 10.1371/journal.ppat.1009638 [doi]
PST - epublish
SO  - PLoS Pathog. 2021 Jun 1;17(6):e1009638. doi: 10.1371/journal.ppat.1009638. 
      eCollection 2021 Jun.