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14th ICID - Poster Abstracts - International Society for Infectious ...

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When citing these abstracts please use the following reference:<br />

Author(s) of abstract. Title of abstract [abstract]. Int J Infect Dis 2010;14S1: Abstract number.<br />

Please note that the official publication of the <strong>International</strong> Journal of <strong>Infectious</strong> Diseases 2010, Volume 14, Supplement 1<br />

is available electronically on http://www.sciencedirect.com<br />

Final Abstract Number: 84.031<br />

Session: Virology and Viral Infections (Non-HIV)<br />

Date: Friday, March 12, 2010<br />

Time: 12:30-13:30<br />

Room: <strong>Poster</strong> & Exhibition Area/Ground Level<br />

Type: <strong>Poster</strong> Presentation<br />

Regulation of poly(A) binding protein during herpes simplex virus infection<br />

O. G. Larralde-Diaz 1 , R. W. P. Smith 2 , P. Malik 3 , S. V. Graham 4 , N. K. Gray 2<br />

1 NHS, Scottish National Blood Transfusion Service, Edinburgh, United Kingdom, 2 Queens<br />

Medical Research Institute, Edinburgh, United Kingdom, 3 University of Edinburgh, Edinburgh,<br />

United Kingdom, 4 University of Glasgow, Glasgow, United Kingdom<br />

Background: The herpes simplex virus (HSV) ICP27 protein is an essential IE protein,<br />

conserved through the Herpesviridae family, that constitutes a target <strong>for</strong> the development of<br />

antiviral drugs and vaccines. ICP27 is a key regulator of viral and cellular gene expression, with<br />

most of its activities in the nucleus.<br />

Methods: The regions of ICP27-PABP1 interaction were mapped by GST pull down and<br />

immunoprecipitation, using a panel of recombinant HSV. PABP1 phosphorylation was studied by<br />

2D-electrophoresis, while shuttling activity was shown by confocal microscopy. Tether function<br />

assay in Xenopus eggs was used to study ICP27 effects in translation, independtly of its nuclear<br />

activities.<br />

Results: ICP27-PABP1 interaction is partially affected by RNAse I treatment in vivo, which could<br />

be explained by the ability of both proteins to <strong>for</strong>m multimers with RNA. Both purified proteins are<br />

able to interact directly in vitro in the presence of RNAse I. The C-terminal of ICP27 is required <strong>for</strong><br />

this interaction, while PABP1 interacted through RRM1-2 and C terminal. We described here a<br />

novel role <strong>for</strong> ICP27 in the cytoplasm, where it stimulates translation. We showed that PABP1<br />

activity is regulated early in HSV infection by phosphorylation, mediated by HSV UL13 kinase.<br />

These events may cause redistribution of ICP27 from the cytoplasm to the nucleus late in<br />

infection.<br />

Conclusion: Our results showed that PABP1 activity is regulated during HSV-1 infection by<br />

phosphorylation and relocalisation, events that seems to be linked to translation regulation.<br />

Experiments to elucidate the mechanism of translational control exerted by ICP27 are currently<br />

under investigation.

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