This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rodrigues, L.
Right arrow Articles by Simas, J. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rodrigues, L.
Right arrow Articles by Simas, J. P.

 Previous Article  |  Next Article 

Journal of Virology, June 2006, p. 6123-6135, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02700-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Activation of Vav by the Gammaherpesvirus M2 Protein Contributes to the Establishment of Viral Latency in B Lymphocytes

Lénia Rodrigues,1,2 Marta Pires de Miranda,1,2 María J. Caloca,3 Xosé R. Bustelo,3* and J. Pedro Simas1,2*

Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal,1 Instituto de Microbiologia e Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal,2 Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer (IBMCC) and Red Temática Cooperativa de Centros de Cáncer, CSIC-University of Salamanca, Campus Unamuno, E-37007 Salamanca, Spain3

Received 20 December 2005/ Accepted 5 April 2006

Gammaherpesviruses subvert eukaryotic signaling pathways to favor latent infections in their cellular reservoirs. To this end, they express proteins that regulate or replace functionally specific signaling proteins of eukaryotic cells. Here we describe a new type of such viral-host interaction that is established through M2, a protein encoded by murine gammaherpesvirus 68. M2 associates with Vav proteins, a family of phosphorylation-dependent Rho/Rac exchange factors that play critical roles in lymphocyte signaling. M2 expression leads to Vav1 hyperphosphorylation and to the subsequent stimulation of its exchange activity towards Rac1, a process mediated by the formation of a trimolecular complex with Src kinases. This heteromolecular complex is coordinated by proline-rich and Src family-dependent phosphorylated regions of M2. Infection of Vav-deficient mice with gammaherpesvirus 68 results in increased long-term levels of latency in germinal center B lymphocytes, corroborating the importance of the M2/Vav cross talk in the process of viral latency. These results reveal a novel strategy used by the murine gammaherpesvirus family to subvert the lymphocyte signaling machinery to its own benefit.

* Corresponding author. Mailing address for J. Pedro Simas: Faculdade de Medicina, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal. Phone: 351 21 799 9417. Fax: 351 21 799 9459. E-mail: psimas{at}fm.ul.pt. Mailing address for Xosé R. Bustelo: Centro de Investigación del Cáncer, CSIC-University of Salamanca, Campus Unamuno, E37007 Salamanca, Spain. Phone: 34-923294802. Fax: 34-923294743. E-mail: xbustelo{at}usal.es.

Journal of Virology, June 2006, p. 6123-6135, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02700-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Stevenson, P. G., Simas, J. P., Efstathiou, S. (2009). Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4. J. Gen. Virol. 90: 2317-2330 [Abstract] [Full Text]  
  • Caloca, M. J., Zugaza, J. L., Bustelo, X. R. (2008). Mechanistic Analysis of the Amplification and Diversification Events Induced by Vav Proteins in B-lymphocytes. J. Biol. Chem. 283: 36454-36464 [Abstract] [Full Text]  
  • DeZalia, M., Speck, S. H. (2008). Identification of Closely Spaced but Distinct Transcription Initiation Sites for the Murine Gammaherpesvirus 68 Latency-Associated M2 Gene. J. Virol. 82: 7411-7421 [Abstract] [Full Text]  
  • Forrest, J. C., Speck, S. H. (2008). Establishment of B-Cell Lines Latently Infected with Reactivation-Competent Murine Gammaherpesvirus 68 Provides Evidence for Viral Alteration of a DNA Damage-Signaling Cascade. J. Virol. 82: 7688-7699 [Abstract] [Full Text]  
  • Herskowitz, J. H., Siegel, A. M., Jacoby, M. A., Speck, S. H. (2008). Systematic Mutagenesis of the Murine Gammaherpesvirus 68 M2 Protein Identifies Domains Important for Chronic Infection. J. Virol. 82: 3295-3310 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»