دورية أكاديمية

Cell Cycle-Dependent Expression of Adeno-Associated Virus 2 (AAV2) Rep in Coinfections with Herpes Simplex Virus 1 (HSV-1) Gives Rise to a Mosaic of Cells Replicating either AAV2 or HSV-1

التفاصيل البيبلوغرافية
العنوان: Cell Cycle-Dependent Expression of Adeno-Associated Virus 2 (AAV2) Rep in Coinfections with Herpes Simplex Virus 1 (HSV-1) Gives Rise to a Mosaic of Cells Replicating either AAV2 or HSV-1
المؤلفون: Franzoso, Francesca D., Seyffert, Michael, Vogel, Rebecca, Yakimovich, Artur, de Andrade Pereira, Bruna, Meier, Anita F., Sutter, Sereina O., Tobler, Kurt, Vogt, Bernd, Greber, Urs F., Büning, Hildegard, Ackermann, Mathias, Fraefel, Cornel
المساهمون: Longnecker, Richard M., Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
المصدر: Journal of Virology ; volume 91, issue 15 ; ISSN 0022-538X 1098-5514
بيانات النشر: American Society for Microbiology
سنة النشر: 2017
الوصف: Adeno-associated virus 2 (AAV2) depends on the simultaneous presence of a helper virus such as herpes simplex virus 1 (HSV-1) for productive replication. At the same time, AAV2 efficiently blocks the replication of HSV-1, which would eventually limit its own replication by diminishing the helper virus reservoir. This discrepancy begs the question of how AAV2 and HSV-1 can coexist in a cell population. Here we show that in coinfected cultures, AAV2 DNA replication takes place almost exclusively in S/G 2 -phase cells, while HSV-1 DNA replication is restricted to G 1 phase. Live microscopy revealed that not only wild-type AAV2 (wtAAV2) replication but also reporter gene expression from both single-stranded and double-stranded (self-complementary) recombinant AAV2 vectors preferentially occurs in S/G 2 -phase cells, suggesting that the preference for S/G 2 phase is independent of the nature of the viral genome. Interestingly, however, a substantial proportion of S/G 2 -phase cells transduced by the double-stranded but not the single-stranded recombinant AAV2 vectors progressed through mitosis in the absence of the helper virus. We conclude that cell cycle-dependent AAV2 rep expression facilitates cell cycle-dependent AAV2 DNA replication and inhibits HSV-1 DNA replication. This may limit competition for cellular and viral helper factors and, hence, creates a biological niche for either virus to replicate. IMPORTANCE Adeno-associated virus 2 (AAV2) differs from most other viruses, as it requires not only a host cell for replication but also a helper virus such as an adenovirus or a herpesvirus. This situation inevitably leads to competition for cellular resources. AAV2 has been shown to efficiently inhibit the replication of helper viruses. Here we present a new facet of the interaction between AAV2 and one of its helper viruses, herpes simplex virus 1 (HSV-1). We observed that AAV2 rep gene expression is cell cycle dependent and gives rise to distinct time-controlled windows for HSV-1 replication. High Rep ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1128/jvi.00357-17
DOI: 10.1128/JVI.00357-17
الإتاحة: https://doi.org/10.1128/jvi.00357-17Test
حقوق: https://journals.asm.org/non-commercial-tdm-licenseTest
رقم الانضمام: edsbas.7C18A36A
قاعدة البيانات: BASE