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Journal of Virology, December 2008, p. 12543-12554, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01215-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus Protein pp71 Displaces the Chromatin-Associated Factor ATRX from Nuclear Domain 10 at Early Stages of Infection{triangledown}

Vera Lukashchuk,{dagger} Steven McFarlane,{dagger} Roger D. Everett, and Chris M. Preston*

Medical Research Council Virology Unit, Church Street, Glasgow, G11 5JR, Scotland, United Kingdom

Received 12 June 2008/ Accepted 6 October 2008

The human cytomegalovirus (HCMV) tegument protein pp71, encoded by gene UL82, stimulates viral immediate-early (IE) transcription. pp71 interacts with the cellular protein hDaxx at nuclear domain 10 (ND10) sites, resulting in the reversal of hDaxx-mediated repression of viral transcription. We demonstrate that pp71 displaces an hDaxx-binding protein, ATRX, from ND10 prior to any detectable effects on hDaxx itself and that this event contributes to the role of pp71 in alleviating repression. Introduction of pp71 into cells by transfection, infection with a pp71-expressing herpes simplex virus type 1 vector, or by generation of transformed cell lines promoted the rapid relocation of ATRX from ND10 to the nucleoplasm without alteration of hDaxx levels or localization. A pp71 mutant protein unable to interact with hDaxx did not affect the intranuclear distribution of ATRX. Infection with HCMV at a high multiplicity of infection resulted in rapid displacement of ATRX from ND10, the effect being observed maximally by 2 h after adsorption, whereas infection with the UL82-null HCMV mutant ADsubUL82 did not affect ATRX localization even at 7 h postinfection. Cell lines depleted of ATRX by transduction with shRNA-expressing lentiviruses supported increased IE gene expression and virus replication after infection with ADsubUL82, demonstrating that ATRX has a role in repressing IE transcription. The results show that ATRX, in addition to hDaxx, is a component of cellular intrinsic defenses that limit HCMV IE transcription and that displacement of ATRX from ND10 by pp71 is important for the efficient initiation of viral gene expression.

* Corresponding author. Mailing address: Medical Research Council Virology Unit, Church Street, Glasgow G11 5JR, Scotland, United Kingdom. Phone: 44 141 330 3921. Fax: 44 141 330 3520. E-mail: c.preston{at}mrcvu.gla.ac.uk

{triangledown} Published ahead of print on 15 October 2008.

{dagger} V.L. and S.M. contributed equally to the work.

Journal of Virology, December 2008, p. 12543-12554, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01215-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Groves, I. J., Reeves, M. B., Sinclair, J. H. (2009). Lytic infection of permissive cells with human cytomegalovirus is regulated by an intrinsic 'pre-immediate-early' repression of viral gene expression mediated by histone post-translational modification. J. Gen. Virol. 90: 2364-2374 [Abstract] [Full Text]  
  • Hwang, J., Kalejta, R. F. (2009). Human Cytomegalovirus Protein pp71 Induces Daxx SUMOylation. J. Virol. 83: 6591-6598 [Abstract] [Full Text]  


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