Elina Zuñiga
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A major challenge in biomedical research is to boost the host defense against infections. Key to this question, which has the potential to unlock ground-breaking new therapeutic strategies, is the appreciation that protection against microbial agents relies on the unique ability of Dendritic cells (DCs), the most powerful antigen presenting cells, to orchestrate innate and adaptive immunity. However, many viruses that cause diseases in humans and present a major health problem, such as measles (MV), dengue and human immunodeficiency virus (HIV), take advantage of the crucial role of DCs, and interfere with their functions in order to evade immune surveillance. Our general research interest is to study DCs in innate and adaptive responses during viral infections, their significance for pathogen clearance and how to modulate or recover DC functions for the benefit of the host.
We study DC-virus interplay by using Lymphocytic Choriomeiningitis virus (LCMV) infection of its natural host, the mouse, as a model system. LCMV is the prototypic member of the family Arenaviridae, which includes many important human pathogens such as Lassa and Junin hemorrhagic fever viruses. Moreover, LCMV infection can 
serve as a powerful model to study virus-immune system interactions because of the natural murine host, easy manipulation of the virus and host immune response, knowledge of immune genetics and the availability of mice modified in several genes of interest.
We use two variants of LCMV with differential ability to replicate within DCs that upon inoculation into adult mice cause acute and chronic infection, respectively. Infection of mice with LCMV Armstrong 53b (ARM) results in an acute infection in which the virus is cleared by cytotoxic T lymphocytes within 7 to 10 days. In contrast, mice infected with the LCMV Clone 13 (Cl 13) variant, which exhibits high replication within DCs, initiates an abortive T cell program that results in a persistent infection and generalized immunosuppression (Figure 1).
By using functional assays and high throughput analysis of gene expression profile we are engaged in an in depth characterization of the molecular determinant of DCs in this model viral infections. These studies will increase our basic understanding of DC innate and adaptive functions during both a successful immune response that results in rapid viral clearance and a suboptimal response that enables viral persistence. We believe that the information gathered from our research will contribute to harness DCs for immune-intervention in order to shift the balance towards anti-viral response and pathogen clearance to treat human viral infections.
CV Rothlin, S Ghosh, E Zúñiga, MBA Oldstone and G Lemke. (2007). TAM receptors are pleiotropic inhibitors of the innate immune response. Cell. In press. (S.G. and E.Z. contributed equally to this work)
E Zúñiga, B Hahm and MBA Oldstone. (2007). Type I interferon during viral infections: multiple triggers for a multifunctional mediator. Current Topics in Microbiology and Immunology. 316:337.
L Martínez-Sobrido, E Zúñiga, A García-Sastre and JC de la Torre. (2006). Inhibition of the type I interferon response by the nucleoprotein of the prototypic arenavirus Lymphocytic Choriomeningitis Virus. Journal of Virology. 80(18):9192.
H Lauterbach, E Zúñiga, P Truong , MBA Oldstone , DB McGavern. (2006). Adoptive immunotherapy induces CNS dendritic cell recruitment and antigen presentation during clearance of a persistent viral infection. Journal of Experimental Medicine. 203(8):1963. (H.L and E.Z. contributed equally to this work).
B Hahm, M Trifilo, E Zúñiga, and MBA Oldstone. (2005). Virus-induced suppression of the immune system through type I interferon-mediated stat2-dependent but stat1-independent signaling. Immunity. 22(2):247.
E Zúñiga, DB McGavern, JL Pruneda-Paz, C Teng and MBA Oldstone. (2004). Bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection. Nature Immunology. 5(12): 1227 (selected for the cover of Nature Immunology issue December 2004 and commented in News and Views section in Nature Immunology, 2004, 5 (12):1206).
Elina Zuniga received her Ph.D. in Chemistry from the Universidad Nacional de Córdoba, Argentina. She conducted postdoctoral research at the Scripps Research Institute before joining the faculty at UCSD.
