Faculty, Graduate Program
Work in our laboratory is focused on two areas. One is the investigation of the molecular mechanisms whereby viruses can persist in the central nervous system (CNS) of the infected host, and cause altered brain function in the absence of overt cytolysis and inflammation. For this purpose we use as model systems the prototypic arenavirus LCMV and the novel neurotropic infectious agent Borna disease virus (BDV). We are using DNA array-based (chip) technology and open-system PCR-based methods to identify genes with altered CNS expression during persistence by LCMV and BDV. We have identified virally-induced disturbances in gene expression of cytokines, neurotrophins, synaptic molecules, and astrocyte functions required to maintain brain homeostasis. To examine the contribution of these identified targets to virus-induced CNS neurodevelopmental and behavioral disturbances, we are using a variety of culture cell systems and animal models. The other area of research is focused on the investigation of the molecular and cellular biology of BDV and LCMV. We have established a robust reverse genetic system for LCMV. We are now in a position to conduct a detailed molecular characterization of the cis-acting signals controlling LCMV RNA synthesis, and to probe the function of viral polypeptides in virus replication, control of gene expression, assembly and budding, as well as their interactions with host cell factors. We are pursuing similar approaches with BDV. Arenaviruses include members that are highly pathogenic for human, such as Lassa fever virus and several newly recognized viral hemorrhagic fevers. On the other hand there is evidence that BDV, or a related virus, can infect humans and might be associated with certain neuropsychiatric disorders. The establishment of robusts reverse genetic systems for LCMV and BDV will provide us with a platform to assess new antiviral strategies against these, and related, viruses.
Ph.D., Autonomous University of Madrid, 1985
de la Torre, J.C. Bornaviridae. In Fields Virology, Fourth Edition, D. Knipe and P. Howley, eds., Lippincott, Williams and Wilins. 2001.
Perez, M, Sanchez, A, Cubitt, B, Rosario, D and de la Torre, J.C. Reverse Genetics for Borna Disease Virus. J.Gen Virol. 84: 3099-3104, 2003.
Perez M, Craven RC, de la Torre J.C. The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. Proc Natl Acad Sci U S A. 100:12978-83, 2003.
Pinschewer DD, Perez M, Sanchez AB, de la Torre J.C. Recombinant lymphocytic choriomeningitis virus expressing vesicular stomatitis virus glycoprotein. Proc Natl Acad Sci U S A. 100:7895-900, 2003.