Patogénese Viral

Interesse da Investigação

Herpesviruses are a major cause of disease worldwide and are among the most accomplished human pathogens, with specific viruses infecting more than 90% of the world population. Their main biological feature is their ability to persist and reactivate in a primed immunocompetent host. The control of herpesvirus infections thus represents an important clinical goal. To achieve this we must understand the basic mechanisms of viral pathogenesis. The overall aim of the viral pathogenesis unit is to gain an understanding of basic molecular mechanisms of the modulation of cellular function and immune evasion afforded by herpesviruses. To this end, we use a laboratory animal model of infection. Our model consists of infection of laboratory mice with murine gamma-herpesvirus-68 (MHV-68) that establishes latent infection in B-lymphocytes. The ability to genetically manipulate both the virus and the host offers the potential to dissect the molecular mechanisms, involved in the virus/host interplay.

Publicações

Jensen, K.K., Chen, S.C., Hipkin, R.W., Wiekowski, M.T., Schwarz, M.A., Chou, C.C., Simas, J., Alcami, A., Lira, S.A. (2003). Disruption of CCL21-induced chemotaxis in vitro and in vivo by M3, a chemokine-binding protein encoded by murine gammaherpesvirus 68. Journal of Virology 77 :624-30

Marques, S., Efstathiou, S., Smith, K.G.C., Haury, M.and Simas, J.P. (2003). Selective Gene Expression of Latent Murine Gammaherpesvirus 68 in B Lymphocytes. Journal of Virology 77 :7308-7318

Orge, L., Galo, A., Sepúlveda, N., Simas, J.P.*, Pires, M. (2003). Scrapie genetic susceptibility in Portuguese sheep breeds. Veterinary Record 153 :508

Fowler, P., Marques, S., Simas, J.P. and Efstathiou, S. (2003). ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency. Journal of General Virology 84 :3405-3416

Stevenson, P.G., May, J.S., Smith, X.G., Marques, S., Adler, H., Koszinowski, U.H., Simas, J.P. and Efstathiou, S. (2002). CD8+ T cell evasion by K3 plays a critical role in the amplification of a latent g-herpesvirus Nature Immunology 3 :733-40

Bridgeman, A., Stevenson, P., Simas, J.P., Efstathiou, S. (2001). A secreted chemokine binding protein encoded by murine gammaherpesvirus 68 is necessary for the establishment of a normal latent load. Journal of Experimental Medicine 194 :1-13

Parry, C.N., Simas, J.P., Smith, V.P., Stewart, C.A., Minson, A.C., Efstathiou, S., Alcami, A. (2000). A broad spectrum secreted chemokine binding protein encoded by a herpesvirus. Journal of Experimental Medicine 191 :573-578

Orge, L., Simas, J.P., Fernandes, A.C., Ramos, M., Galo, A. (2000). The lesion profile of BSE in Portuguese cattle is similar to that described in British cattle. Veterinary Record 147 :486-488

Simas, J.P., Swann, D., Bowden, R., Efstathiou, S. (1999). Analysis of murine gammaherpesvirus-68 transcription during lytic and latent infection. Journal of General Virology 80 :75-82

Donnelly, C.A., Santos, R., Ramos, M., Galo, A., Simas, J.P. (1999). BSE in Portugal: Anticipating the decline of an Epidemic. Journal of Epidemiology and Biostatistics 4 :277-283

Simas, J.P., Bowden, R.J., Paige, V., Efstathiou, S. (1998). Four tRNA-like sequences and a serpin homologue encoded by murine gammaherpesvirus 68 are dispensable for lytic replication in vitro and latency in vivo Journal of General Virology 79 :149-53

Simas, J.P., Efstathiou, S. (1998). Murine gammaherpesvirus 68: a model for the study of gammaherpesvirus pathogenesis Trends in Microbiology 6 :276-82

Bowden, R.J., Simas, J.P., Davis, A.J., Efstathiou, S. (1997). Murine gammaherpesvirus 68 encodes tRNA-like sequences which are expressed during latency Journal of General Virology 78 :1675-87

Simas, J.P., Fazakerley, J.K. (1996). The course of disease and persistence of virus in the central nervous system varies between individual CBA mice infected with the BeAn strain of Theiler's murine encephalomyelitis virus Journal of General Virology 77 :2701-11

Simas, J.P., Dyson, H. and Fazakerley, J.K. (1995). The neurovirulent GDVII strain of Theiler¹s virus can replicate in glial cells Journal of Virology 69 :5599-5606