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Acta Physiologica Congress

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Acta Physiologica 2009; Volume 195, Supplement 669
The 88th Annual Meeting of The German Physiological Society
3/22/2009-3/25/2009
Giessen, Germany


DELIVERY OF HERPES SIMPLEX VIRUS TYPE 1 GENOME THROUGH THE NUCLEAR PORE COMPLEX
Abstract number: O333

Liashkovich1 I., Hafezi2 W., Kuehn2 K., Oberleithner1 H., Kramer1 A., Shahin1 V.

1Institute of Physiology II, Mnster
2Institute of Medical Microbiology, Mnster

Herpes simplex virus type 1 (HSV-1) is a highly contagious, widespread human pathogen infecting more than 80% of the adult population worldwide. It can cause a variety of diseases some of which may be life threatening. Once a person has been infected with HSV-1 it remains there forever. The replication of HSV-1 involves an essential process in which the incoming capsid uncoats to deliver the viral genome into the nucleus of the infected cell. Uncoating occurs when a large capsid (125 nm in diameter) binds to a 100 nm wide nuclear pore complex (NPC) and delivers its large (152 kbp, 45 mm long) DNA through the 10 nm wide and 50 nm long NPC channel into the nucleoplasm. The question remains unanswered, however, as to how the viral genome overcomes the tight NPC channel barrier. Structural similarity of HSV-1 to large bacteriophages implies that HSV-1 uncoating might be pressure-driven. To explore this possibility a nano-approach, atomic force microscopy (AFM), was applied. AFM enables structural and mechanical investigations on biological samples at the nanoscale, very importantly in physiological environments. Using AFM, we visualised and simultaneously performed nano-indentation measurements on genome-containing and genome-free capsids. The genome-containing HSV-1 capsids was found to withstand an exceptionally large mechanical force of ~6 nN which is three times larger than the highest values previously reported for any other viruses. Greater mechanical forces, however, lead to a release of the viral genome. To conclude, HSV-1 capsids exhibit an exceptional structural and mechanical stability which is largely provided by the densely packaged genome. This in turn indicates that the viral genome is pressurised inside the capsid. It is conceivable that once the incoming capsid opens up on binding to the NPC, genome release will occur fast pressure-driven. In addition, the exceptional mechanical stability of the HSV-1 capsid might be the key determinant for it's survival over long distances in the axonal cytoplasm where it is exposed to mechanical forces by molecular motors before it reaches the NPC for the crucial genome uncoating.

To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 669 :O333

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