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Acta Physiologica Congress

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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany


HOW DOES THE HERPES SIMPLEX VIRUS GENOME OVERCOME THE TIGHT NUCLEAR BARRIER?
Abstract number: O12

Meyring 1   *A. , Liashkovich 1  I., Hafezi 2  W., Kühn 2  J., Shahin 1  V.

1 University of Münster, Institute of Physiology II, Münster, Germany
2 University of Münster, Institute of Medical Microbiology, Münster, Germany

The replication of Herpes simplex virus type 1 (HSV-1) genome takes place in the host cell nucleus. To do so, the viral genome must cross the nuclear envelope through nuclear pore complexes (NPCs). This enigmatic process, called uncoating, is believed to involve the following steps: First, the incoming 125 nm wide icosohedral capsid pinpoints the 100 nm wide NPC. It then opens up at the NPC to release the viral genome through the NPC into the nucleoplasm. To date, it remains unclear how the 50 µm long genome translocates through the dense, 50 nm long NPC channel. To be able to unravel nuclear delivery of HSV-1 genome at the nano-scale, importantly in physiological conditions, a development of a challenging assay is required. We established an assay that bases on microinjection of HSV-1 capsids into Xenopus laevis oocytes. Microinjection is followed by isolation of the delicate nuclear envelope. In addition, the nuclear envelope is prepared in a way so that both the cytoplasmic and nucleoplasmic faces can be investigated at the same time. Based on our observations, we conclude that the HSV-1 capsid targets the NPC and docks at its center. It then releases the genome which translocates through the NPC as a flexible rope-like structure. Furthermore, once the genome enters the nucleus it is covered by nuclear proteins whose identity remains unclear yet. Finally, our approach is not limited to HSV-1 genome but can be extended for investigating nuclear delivery of genomes of other viruses.

To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :O12

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