Pedro Simas Lab
The overall aim of the Viral Pathogenesis Unit is to gain an understanding of the basic molecular mechanisms involved in the modulation of cellular function by herpesviruses. Herpesviruses are a major cause of disease worldwide and are amongst the most successful human pathogens, with specific viruses infecting more than 90% of the world's population. The main biological feature of these viruses is their ability to persist and reactivate in a primed immunocompetent host. The control of herpesviruses infections thus represents an important clinical goal. To achieve this we must first understand the basic mechanisms of viral pathogenesis. We use a laboratory animal model of infection with murine gamma-herpesvirus-68 (MHV-68), which establishes latent infection in B-lymphocytes. The ability to genetically manipulate both the virus and the host allows the dissection of the molecular mechanisms involved in the virus/host interaction.
We have recently identified viral proteins that are essential for the effective establishment of latent infection. One of these, M2, functions as an adaptor protein that assembles a signalosome with cellular proteins involved in the activation and differentiation of B lymphocytes, and which we have shown to be essential for the establishment of latent infection.
» Research Areas
» Group Leader
» Research Team
PhD (1994) in Viral Pathogenesis at the University of Cambridge, UK
Post-doctoral research at the University of Cambridge, UK
Principal Investigator at the Instituto Gulbenkian Ciência (until 1999)
Associate Professor at the Faculty of Medicine, University of Lisbon
» Ongoing Research Projects
2007/10 - Herpesvirus-encoded microRNAs as novel regulators of host gene expression: molecular function during latent infection in B-lymphocytes, (PTDC/SAU-MII/65017/2006).
» Science and Society Activities
Drs. Stacey Efstathiou and Philip Stevenson (Division of Virology, Department of Pathology, University of Cambridge, UK)
Prof. Xosé Bustelo (Centro de Investigación del Cáncer, Universidad de Salamanca, Espanha)
Dr. Kenneth Kaye (Harvard Medical School, USA)
» Selected Publications
» Useful Links
Stevenson PG, Simas JP, Efstathiou S. Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4. J Gen Virol. 2009 Oct;90(Pt 10):2317-30. Epub 2009 Jul 15. Review.
Rodrigues L, Filipe J, Seldon MP, Fonseca L, Anrather J, Soares MP, Simas JP. Termination of NF-kappaB activity through a gammaherpesvirus protein that assembles an EC5S ubiquitin-ligase. EMBO J. 2009 May 6;28(9):1283-95. Epub 2009 Mar 26.
Milho R, Smith CM, Marques S, Alenquer M, May JS, Gillet L, Gaspar M, Efstathiou S, Simas JP, Stevenson PG. In vivo imaging of murid herpesvirus-4 infection. J Gen Virol. 2009 Jan;90(Pt 1):21-32.
Marques S, Alenquer M, Stevenson PG, Simas JP. A single CD8+ T cell epitope sets the long-term latent load of a murid herpesvirus. PLoS Pathog. 2008 Oct;4(10):e1000177. Epub 2008 Oct 10.
Pires de Miranda M, Alenquer M, Marques S, Rodrigues L, Lopes F, Bustelo XR, Simas JP. The Gammaherpesvirus m2 protein manipulates the Fyn/Vav pathway through a multidocking mechanism of assembly. PLoS One. 2008 Feb 27;3(2):e1654.
Rodrigues L, Pires de Miranda M, Caloca MJ, Bustelo XR, Simas JP. Activation of Vav by the gammaherpesvirus M2 protein contributes to the establishment of viral latency in B lymphocytes. J Virol. 2006 Jun;80(12):6123-35.
Orge L, Galo A, Machado C, Lima C, Ochoa C, Silva J, Ramos M, Simas JP. Identification of putative atypical scrapie in sheep in Portugal. J Gen Virol. 2004 Nov;85(Pt 11):3487-91.
Simas JP, Marques S, Bridgeman A, Efstathiou S, Adler H. The M2 gene product of murine gammaherpesvirus 68 is required for efficient colonization of splenic follicles but is not necessary for expansion of latently infected germinal centre B cells. J Gen Virol. 2004 Oct;85(Pt 10):2789-97.
Marques S, Efstathiou S, Smith KG, Haury M, Simas JP. Selective gene expression of latent murine gammaherpesvirus 68 in B lymphocytes. J Virol. 2003 Jul;77(13):7308-18.