Fernando A. Osorio, DVM, PhD, DACVM
Research Interests: My research centers on pathogenesis of and immune response to viral infections. Due to the significance of the subject for U.S. animal agriculture, we focus on a major viral agent that affects swine: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV, an arterivirus, ssRNA+ genome). The significance of the Porcine Reproductive and Respiratory Syndrome Syndrome (PRRS) for the U.S. animal agriculture can not be overemphasized. Preliminary results from a Pork Checkoff-sponsored study indicate that the PRRS is costing the U.S. pork industry over $ 600 million /year . Because of the serious threat posed by PRRS, the swine industry supporting organizations ( NPPC and NPB) are spearheading a national effort targeting the PRRSV. This campaign is helping to establish a collective awareness about the idea of PRRSV being a feasible target for eradication, like Hog Cholera and Pseudorabies have been in the past. The initial step for a complete eradication of PRRSV is first the prevention of infection and its control. We think that one major solution to PRRSV prevention resides in the use of more efficient vaccines that would improve the ones available now. To improve vaccines it is essential to understand the basis of protective immunity against PRRSV. Our laboratory has consistently produced new information that contributed better understanding of the basic foundation of PRRSV protective immunity. We have characterized the immunobiology of persistence of this virus in convalescent animals. Our research indicates that, contrary to other known examples of RNA virus persistence, the persistent infection established by PRRSV is finite and seems to involve a low level of productive infection that progressively declines until complete viral clearance takes place. We found that during the period of viral persistence, extensive modulation of the homologous (PRRSV-specific) cell-mediated and humoral immune response takes place. Current emphasis centers on the role that PRRSV-neutralizing antibodies have in protection against infection and clinical disease. The PRRSV-neutralizing antibodies, that we have shown are a major correlate of protection in the PRRS model, are produced by the host very late in the infection process ( at @ 6 weeks post-infection). The mechanisms of modulation of the protective immune response by PRRSV are currently under investigation in our laboratory. Mechanisms of acquired immunity against PRRSV are of cardinal importance in the improvement of current vaccines, which is the ultimate goal for our lab. From our research it also became clear that attenuated live vaccines can prime the pig’s immune system to produce, upon challenge with wildtype virus, an anamnestic (recall) cross-neutralizing antibody that can fully prevent infection and reproductive failure caused by the PRRSV in the pregnant sows that received the vaccine. Now, taking advantage of an infectious clone we are following a methodical approach to map, using different strategies, the virulence, host range and in vivo tropism of PRRSV. Mapping of virulence genes in PRRS virus should provide essential information to develop differential PRRSV vaccines of unprecedented safety and efficacy. Rational engineering of new live-attenuated PRRSV marker vaccines will require knowledge of the genetic basis of viral virulence and cell tropism and identification of nonessential regions of the viral genome. The infectious cDNA clone is a tool exceptionally appropriate for this task,. The high virulence of this clone, which retains all the in vivo virulence and transmissibility properties of the parental strain, positions us now to address a fundamental question: What is the molecular basis of attenuation of virulence in PRRSV? To answer this query, we are following a systematic molecular characterization of the virulent phenotype of PRRSV so as to identify the genetic markers of virulence in PRRSV and to obtain, at the end, better attenuated strains to be used as vaccines. Considering that vaccination against PRRSV infection is a multi-billion enterprise worldwide and that a better vaccine (safer and more efficacious) is badly needed, we are certain that our aim should have significant wide impact . Selected Recent Publications : de Lima, M. Ansari, I. H., Das, P. B., Ku, B., Martinez-Lobo, F. J., Pattnaik, A. K., and Osorio, F. A. (2009). GP3 is a Structural Component of the PRRSV Type II Virion. Virology, 390:31-36 Jar, A.M., Osorio, F.A., Lopez, O.J. (2009 )Mouse x pig chimeric antibodies expressed in baculovirus retain the same properties of their parent antibodies. Biotechnology Progress Mar-Apr;25(2):516-235 Beura, L. K., Sarkar, S. N., Kwon, B. J., Subramaniam, S., Jones, C., Pattnaik, A. K., and Osorio, F. A. (2010). Porcine Reproductive and Respiratory Syndrome Virus nonstructural protein nsp1b modulates host immune response by antagonizing IRF3 activation. J. Virology In press Das, P. B., Dinh, P. X., Ansari, I. H., de Lima, M., Osorio, F. A., and Pattnaik, A. K. (2010). The Minor Envelope Glycoproteins GP2a and GP4 of Porcine Reproductive and Respiratory Syndrome Virus Interact with the Receptor, CD163. J. Virology In press Other publications by Dr. Osorio can be found at List of PubMed-indexed publications |
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