Poly(A)-binding protein 1 (PABP1) partially relocalises to the nucleus during HSV-1 infection in an ICP27-independent manner and does not inhibit virus replication

Salaun, C., MacDonald, A.I., Larralde, O., Howard, L., Lochtie, K., Burgess, H.M., Brook, M., Malik, P., Gray, N.K. and Graham, S.V. (2010) Poly(A)-binding protein 1 (PABP1) partially relocalises to the nucleus during HSV-1 infection in an ICP27-independent manner and does not inhibit virus replication. Journal of Virology, 84(17), pp. 8539-8548. (doi: 10.1128/JVI.00668-10) (PMID:20573819) (PMCID:PMC2919032)

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Abstract

Infection of cells by herpes simplex virus type 1 (HSV-1) triggers host cell shut-off whereby mRNAs are degraded and cellular protein synthesis is diminished. However virus protein translation continues because the translational apparatus in HSV-infected cells is maintained in an active state. Surprisingly, poly(A)-binding protein 1 (PABP1) a predominantly cytoplasmic protein that is required for efficient translation initiation, is partially relocated to the nucleus during HSV-1 infection. This relocalisation occurred in a time-dependent manner with respect to virus infection. Since HSV-1 infection causes cell stress, we examined other cell stress inducers and found that oxidative stress similarly relocated PABP1. Examination of stress-induced kinases revealed similarities in HSV-1 infection and oxidative stress activation of Jnk and p38 MAP kinases. Importantly, PABP relocalisation in infection was found to be independent of the viral protein ICP27. Depletion of PABP1 by siRNA knock-down had no significant effect on viral replication or expression of selected virus late proteins suggesting that reduced levels of cytoplasmic PABP1 are tolerated during infection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Graham, Professor Sheila and Salaun, Dr Christine and MacDonald, Dr Alasdair
Authors: Salaun, C., MacDonald, A.I., Larralde, O., Howard, L., Lochtie, K., Burgess, H.M., Brook, M., Malik, P., Gray, N.K., and Graham, S.V.
Subjects:Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Virology
Journal Abbr.:J. Virol.
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514
Published Online:23 June 2010

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
380311A family of multifunctional proteins that orchestrates RNA metabolism in herpesvirus infected cellsSheila GrahamMedical Research Council (MRC)G9826324Centre for Virus Research