Universität zu Köln

Seyffert, Michael ORCID: 0000-0001-7483-2430, Glauser, Daniel L., Schraner, Elisabeth M., de Oliveira, Anna-Paula, Mansilla-Soto, Jorge, Vogt, Bernd, Buening, Hildegard, Linden, R. Michael, Ackermann, Mathias and Fraefel, Cornel ORCID: 0000-0001-7221-6706 (2017). Novel Mutant AAV2 Rep Proteins Support AAV2 Replication without Blocking HSV-1 Helpervirus Replication. PLoS One, 12 (1). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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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 Rep-helicase 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Seyffert, Michael UNSPECIFIED orcid.org/0000-0001-7483-2430 UNSPECIFIED Glauser, Daniel L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schraner, Elisabeth M. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Oliveira, Anna-Paula UNSPECIFIED UNSPECIFIED UNSPECIFIED Mansilla-Soto, Jorge UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogt, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Buening, Hildegard UNSPECIFIED UNSPECIFIED UNSPECIFIED Linden, R. Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Ackermann, Mathias UNSPECIFIED UNSPECIFIED UNSPECIFIED Fraefel, Cornel UNSPECIFIED orcid.org/0000-0001-7221-6706 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-242189
DOI:	10.1371/journal.pone.0170908
Journal or Publication Title:	PLoS One
Volume:	12
Number:	1
Date:	2017
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ADENOASSOCIATED VIRUS TYPE-2; DNA-DAMAGE RESPONSE; BACTERIAL ARTIFICIAL CHROMOSOME; GREEN FLUORESCENT PROTEIN; SITE-SPECIFIC INTEGRATION; E2A GENE-EXPRESSION; AMPLICON VECTORS; IN-VITRO; ADENOVIRUS REPLICATION; TRANSGENE EXPRESSION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24218