Novel mutant AAV2 rep proteins support AAV2 replication without blocking HSV-1 helpervirus replication Journal Article


Authors: Seyffert, M.; Glauser, D. L.; Schraner, E. M.; De Oliveira, A. P.; Mansilla-Soto, J.; Vogt, B.; Büning, H.; Linden, R. M.; Ackermann, M.; Fraefel, C.
Article Title: Novel mutant AAV2 rep proteins support AAV2 replication without blocking HSV-1 helpervirus replication
Abstract: As their names imply, parvoviruses of the genus Dependovirus rely for their efficient replication on the concurrent presence of a helpervirus, such as herpesvirus, adenovirus, or papilloma virus. Adeno-associated virus 2 (AAV2) is such an example, which in turn can efficiently inhibit the replication of each helpervirus by distinct mechanisms. In a previous study we have shown that expression of the AAV2 rep gene is not compatible with efficient replication of herpes simplex virus 1 (HSV-1). In particular, the combined DNA-binding and ATPase/helicase activities of the Rep68/78 proteins have been shown to exert opposite effects on the replication of AAV2 and HSV-1. While essential for AAV2 DNA replication these protein activities account for the Rep-mediated inhibition of HSV-1 replication. Here, we describe a novel Rep mutant (Rep-D371Y), which displayed an unexpected phenotype. Rep-D371Y did not block HSV-1 replication, but still supported efficient AAV2 replication, at least when a double-stranded AAV2 genome template was used. We also found that the capacity of Rep-D371Y to induce apoptosis and a Rep-specific DNA damage response was significantly reduced compared to wild-type Rep. These findings suggest that AAV2 Rephelicase subdomains exert diverging activities, which contribute to distinct steps of the AAV2 life cycle. More important, the novel AAV2 mutant Rep-D371Y may allow deciphering yet unsolved activities of the AAV2 Rep proteins such as DNA second-strand synthesis, genomic integration or packaging, which all involve the Rep-helicase activity. © 2017 Seyffert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Journal Title: PLoS ONE
Volume: 12
Issue: 1
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2017-01-26
Start Page: e0170908
Language: English
DOI: 10.1371/journal.pone.0170908
PROVIDER: scopus
PMCID: PMC5268427
PUBMED: 28125695
DOI/URL:
Notes: Article -- Export Date: 2 March 2017 -- Source: Scopus
Altmetric
Citation Impact
MSK Authors