دورية أكاديمية
Novel mutant AAV2 rep proteins support AAV2 replication without blocking HSV-1 helpervirus replication
| العنوان: | Novel mutant AAV2 rep proteins support AAV2 replication without blocking HSV-1 helpervirus replication |
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| المؤلفون: | Seyffert, Michael, Glauser, Daniel L, Schraner, Elisabeth M, de Oliveira, Anna-Paula, Mansilla-Soto, Jorge, Vogt, Bernd, Büning, Hildegard, Linden, R. Michael, Ackermann, Mathias, Fraefel, Cornel |
| المصدر: | Seyffert, Michael; Glauser, Daniel L; Schraner, Elisabeth M; de Oliveira, Anna-Paula; Mansilla-Soto, Jorge; Vogt, Bernd; Büning, Hildegard; Linden, R. Michael; Ackermann, Mathias; Fraefel, Cornel (2017). Novel mutant AAV2 rep proteins support AAV2 replication without blocking HSV-1 helpervirus replication. PLoS ONE, 12(1):e0170908. |
| بيانات النشر: | Public Library of Science (PLoS) |
| سنة النشر: | 2017 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Institute of Veterinary Anatomy, Institute of Virology, 570 Life sciences, biology |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| العلاقة: | https://www.zora.uzh.ch/id/eprint/133416/1/PU547.pdfTest; info:pmid/28125695; urn:issn:1932-6203 |
| DOI: | 10.5167/uzh-133416 |
| DOI: | 10.1371/journal.pone.0170908 |
| الإتاحة: | https://doi.org/10.5167/uzh-13341610.1371/journal.pone.0170908Test https://www.zora.uzh.ch/id/eprint/133416Test/ https://www.zora.uzh.ch/id/eprint/133416/1/PU547.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.58BD5D82 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.5167/uzh-133416 |