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Journal of Virology, January 2008, p. 602-608, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01571-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Downregulation of the T-Cell Receptor Complex and Impairment of T-Cell Activation by Human Herpesvirus 6 U24 Protein{triangledown}

Brian M. Sullivan and Laurent Coscoy*

Department of Molecular and Cell Biology, Division of Immunology, University of California, Berkeley, California

Received 18 July 2007/ Accepted 23 October 2007

We have performed a screen aimed at identifying human herpesvirus 6 (HHV-6)-encoded proteins that modulate immune recognition. Here we show that the U24 protein encoded by HHV-6 variant A downregulates cell surface expression of the T-cell receptor (TCR)/CD3 complex, a complex essential to T-cell activation and the generation of an immune adaptive response. In the presence of U24, the TCR/CD3 complex is endocytosed but is not recycled back to the plasma membrane. Instead, it accumulates in early and late endosomes. Interestingly, whereas CD3 downregulation from the cell surface is normally associated with T-cell activation, U24 downregulates CD3 independently of T-cell activation. Moreover, we found that U24-expressing T cells are resistant to activation by antigen-presenting cells. HHV-6 has evolved a unique mechanism of inhibition of T-cell activation that may impair the establishment of an adaptive immune response. Furthermore, lymphocyte activation creates an environment favorable to the reactivation and replication of lymphotropic herpesviruses. Thus, by inhibiting T-cell activation, HHV-6 might limit its reactivation and thus minimize immune recognition.

* Corresponding author. Mailing address: Department of Molecular and Cell Biology, Division of Immunology, 142 LSA, University of California, Berkeley, CA 94720-3200. Phone: (510) 643-4128. Fax: (510) 643-4128. E-mail: lcoscoy{at}berkeley.edu

{triangledown} Published ahead of print on 31 October 2007.

Journal of Virology, January 2008, p. 602-608, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01571-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gupta, S., Agrawal, S., Gollapudi, S. (2009). Differential Effect of Human Herpesvirus 6A on Cell Division and Apoptosis among Naive and Central and Effector Memory CD4+ and CD8+ T-Cell Subsets. J. Virol. 83: 5442-5450 [Abstract] [Full Text]  
  • Jerome, K. R. (2008). Viral Modulation of T-Cell Receptor Signaling. J. Virol. 82: 4194-4204 [Full Text]  


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