التفاصيل البيبلوغرافية
| العنوان: |
Novel Mutant AAV2 Rep Proteins Support AAV2 Replication without Blocking HSV-1 Helpervirus Replication. |
| المؤلفون: |
Seyffert, Michael1,2, Glauser, Daniel L.1, Schraner, Elisabeth M.1,3, de Oliveira, Anna-Paula1, Mansilla-Soto, Jorge4, Vogt, Bernd1, Büning, Hildegard5,6, Linden, R. Michael7, Ackermann, Mathias1, Fraefel, Cornel1 cornel.fraefel@access.uzh.ch |
| المصدر: |
PLoS ONE. 1/26/2017, Vol. 12 Issue 1, p1-21. 21p. |
| مصطلحات موضوعية: |
*PAPILLOMAVIRUS diseases, *HERPES simplex, *DNA replication, *PHENOTYPES, *GENE expression, *GENETICS |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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