Fernando A. Osorio, DVM, PhD, DACVM

Professor
University of Nebraska-Lincoln
School of Veterinary and Biomedical Sciences
111 Morrison Center
Lincoln, NE 68583-0900
Phone - 402.472.7809
Fax - 402.472.3323
E-mail: fosorio1@unl.edu

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. Results from a 2005 Pork Checkoff-sponsored study indicated that the PRRS was costing the U.S. pork industry almost $ 600 million /year. That figure would now be even much higher if the correction for increase of feed cost sience 2005 is applied.

Because of the serious threat posed by PRRS, the organizations supporting swine industry ( NPPC and NPB) are spearheading a national effort targeting the PRRSV. Such campaign , together with swine professional organizations, are helping to establish a collective awareness about the idea of PRRSV being a feasible target for eradication, like Hog Cholera ( Classical Swine Fever) and Pseudorabies have been in the past. The initial step for a complete eradication of PRRSV starts with the prevention of infection and its control.

We think that one major approach to PRRSV prevention resides in the use of more efficient vaccines that would improve the ones available now. To improve the current 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, although finally a firm convalescent immunity gets established and PRRSV is eliminated from the infected pig, although this cure sometimes takes up to 5 months or even more .

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. We found that these mechanisms may involve different strategies of immune evasion,including the display of decoy epitopes and/or glycan shielding of one or more envelope glycoproteins. Mechanisms of acquired immunity against PRRSV are of cardinal importance for 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 responsethat can fully prevent infection and reproductive failure caused by the PRRSV in the pregnant sows that received the vaccine.

Now, taking advantage of a PRRSV 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 fit 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.

In parallel to these studies we are actively pursuing the development of a DIVA marker system ( DIVA means differentiation of vaccinated from infected animals) based on the serological response to well conserved immuno-dominant, non-protective B cell epitopes coded for in the PRRSV genome and which could be applied in the case of the modified live vaccines currently used in the US market.

Considering that vaccination against PRRSV infection is a multi-million dollar 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

Anderson TK, Laegreid WW, Cerutti F, Osorio FA, Nelson EA, Christopher-Hennings J, Goldberg TL.(2012)Ranking viruses: measures of positional importance within networks define core viruses for rational polyvalent vaccine development. Bioinformatics. 2012 Jun 15;28(12):1624-32

Jourdan SS, Osorio FA, Hiscox JA. Biophysical characterization of the nucleocapsid protein from a highly pathogenic porcine reproductive and respiratory syndrome virus strain. Biochem Biophys Res Commun. 2012 Mar 9;419(2):137-41.

Jourdan SS, Osorio F, Hiscox JA.(2012) An interactome map of the nucleocapsid protein from a highly pathogenic North American porcine reproductive and respiratory syndrome virus strain generated using SILAC-based quantitative proteomics. Proteomics. 2012 Apr;12(7):1015-23.

Subramaniam S, Beura LK, Kwon B, Pattnaik AK, Osorio FA.2012.Amino acid residues in the non-structural protein 1 of porcine reproductive and respiratory syndrome virus involved in down-regulation of TNF-α expression in vitro and attenuation in vivo. Virology 432(2): 241-9

Parida, R, Choi IS, Peterson DA, Pattnaik AK, Laegreid W, Zuckermann F and Osorio FA.(2012) Location of T-cell epitopes in nonstructural proteins 9 and 10 of type-II porcine reproductive and respiratory syndrome virus. Virus Research 2012 169(1):13-21

    Beura LK; Subramaniam, S; Vu, HXL; Kwon, BJ; Pattnaik,AK; Osorio FA. 2012. Identification of amino acid residues important for anti-IFN activity of porcine reproductive and respiratory syndrome virus non-structural protein 1. Virology 2012 433(2):431-9.

Vu, H. L., B. J. Kwon, M. de Lima, A. K. Pattnaik, and F. Osorio. 2013. Characterization of a serologic marker candidate for development of a live-attenuated DIVA vaccine against porcine reproductive and respiratory syndrome virus. Vaccine. 2013 Jul 23. pii: S0264-410X

Other publications by Dr. Osorio can be found at List of PubMed-indexed publications

Education

MV (Veterinarian) Buenos Aires National (Argentina), 1972

Masters of Science Iowa State University, 1984

Doctor of Philosophy Iowa State University, 1984

Diplomate, American College of Veterinary Microbiologists. 1986

Professional Positions

1984 to date:
Professor
University of Nebraska-Lincoln, Department of Veterinary and Biomedical Sciences, (Date of Current Rank: July 1995), Previous ranks: Associate Professor (1990-95) and Assistant Professor (1984-90).

1984-2006
Head
Diagnostic Virology, Veterinary Diagnostic Center, Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln

1992-1993
Head
, Reference Laboratory for Vesicular Disease and Vaccine Control for the Americas, and Advisor in Vesicular DiseasesPan-American Foot-and-Mouth Disease Center, Pan American Health Organization W.H.O. Rio de Janeiro Brazil

1973-1979
Researcher , Foot-and-Mouth Disease, Instituto Nacional de Tecnologia            Agropecuaria, Argentina

Honors and Awards

2005 Dermot Coyne Award, in recognition to leadership and outstanding g service to International Students, conferred by International Affairs, University of Nebraska-Lincoln, April 2005

Fulbright Scholar 1997/1998. Teaching and Research, Universidade Federal de Santa Maria, Brazil