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Elina Zuñiga e-mail: eizuniga@ucsd.edu
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Innate and adaptive immunity during viral infections
The immune system is responsible for the tremendous task of fighting a wide range of pathogens to which we are constantly exposed. This system can be broadly subdivided into innate and adaptive arms, which act in conjunction to protect the host. The innate immune system exists in both vertebrate and invertebrate organisms and represents the first barrier against microbial invasion. This arm of the immune system rapidly eliminates the vast majority of microorganisms that we daily encounter and is responsible for limiting early pathogen replication and imprints the profile of the subsequent adaptive response. The adaptive immune response is a more sophisticated feature, found only in vertebrate animals, involving a broad repertoire of genetically rearranged receptors that specifically recognize microbial antigens. The hallmark of the adaptive response is the generation of a potent and long-lasting protection specifically directed against the invading pathogen. Despite these highly evolved immune responses, some pathogens have found ways to evade or subvert the immune system to favor their replication and transmission. Indeed, despite major scientific and medical efforts, infectious diseases remain among the leading causes of mortality and disability worldwide. Dramatic examples of microbial immune-evasion are chronic viral infections such as Human Immunodeficiency virus, Hepatitis B and C viruses, which currently infect about 500 million people around the world.
To determine the strategies used by viruses to establish chronic infections we study cellular and molecular aspects of innate and adaptive immune responses during acute versus chronic viral infections. Our model consists of infecting mice with two genetically related Lymphocytic choriomeningitis virus isolates that differ in few amino acids but induce either a successful immune response that results in rapid viral clearance or an abortive response that enables viral persistence. Although we evaluate different aspects of the anti-viral immune response, our research is centered on dendritic cells, a specialized subset of leukocytes that coordinate innate and adaptive immunity. By using immunological and viral assays, high throughput analysis of gene expression profiles and genetically modified mice we are engaged in an in depth characterization of the molecular determinants of viral persistence and pathogenesis.
R Tinoco, V Alcalde, Y Yang, K Sauer and E Zuñiga. Cell-intrinsic transforming growth factor-b signaling mediates virus-specific CD8+ T cell deletion and viral persistence in vivo. Immunity. 2009. 31(1): 145-157.
E Zuñiga, L Liou, L Mack, M Mendoza and MBA Oldstone. Persistent virus infection inhibits type I interferon production by plasmacytoid dendritic cells to facilitate opportunistic infections. Cell Host Microbe. 2008. 16 (4):374-386.
CV Rothlin, S Ghosh*, E Zuñiga*, MBA Oldstone and G Lemke. TAM receptors are pleiotropic inhibitors of the innate immune response. Cell. 2007. 131 (6):1124. (*Denotes equal contribution)
H Lauterbach*, E Zuñiga*, P Truong , MBA Oldstone , DB McGavern. Adoptive immunotherapy induces CNS dendritic cell recruitment and antigen presentation during clearance of a persistent viral infection. Journal of Experimental Medicine. 2006. 203(8):1963. (*Denotes equal contribution).
B Hahm, M Trifilo, E Zuñiga, and MBA Oldstone. Virus-induced suppression of the immune system through type I interferon-mediated stat2-dependent but stat1-independent signaling. Immunity. 2005. 22(2):247.
E Zuñiga, DB McGavern, JL Pruneda-Paz, C Teng and MBA Oldstone. Bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection. Nature Immunology. 2004. 5(12): 1227.
Elina Zuñiga received her Ph.D. in Biochemistry from the National University of Cordoba, Argentina. She conducted postdoctoral research at The Scripps Research Institute where she was a PEW Fellow. After joining UCSD in 2007 she has received a Hellman Foundation Scholar Award.
