Lukashchuk, V., McFarlane, S., Everett, R.D. and Preston, C.M. (2008) Human cytomegalovirus protein pp71 displaces the chromatin associated factor ATRX from nuclear domain 10 at early stages of infection. Journal of Virology, 82(24), pp. 12543-12554. (doi: 10.1128/JVI.01215-08)
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Publisher's URL: http://dx.doi.org/10.1128/JVI.01215-08
Abstract
The human cytomegalovirus (HCMV) tegument protein pp71, encoded by gene UL82, stimulates viral immediate early (IE) transcription. Pp71 interacts with 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 high moi 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 hours post infection. 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
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Preston, Prof Christopher and Everett, Professor Roger |
| Authors: | Lukashchuk, V., McFarlane, S., Everett, R.D., and Preston, C.M. |
| Subjects: | Q Science > QR Microbiology > QR355 Virology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of Virology |
| Journal Abbr.: | J. Virol. |
| ISSN: | 0022-538X |
| ISSN (Online): | 1098-5514 |
| Published Online: | 15 October 2008 |
| Related URLs: |
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