THIS PROJECT AIMS TO DEVELOP A BETTER AND SUITABLE CONTROL STRATEGY FOR PRRS (PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME). PRRS IS AN EMERGED AND RE-EMERGING DISEASE OF SWINE IN MOST PIG-PRODUCING COUNTRIES INCLUDING THE US. PRRS IS CHARACTERIZED BY ABORTIONS AND FETAL DEATHS IN PREGNANT SOWS/GILTS, AND RESPIRATORY DISEASE IN NURSING AND GROW/FINISH PIGLETS WITH A DECREASED GROWTH RATE AND INCREASED MORTALITY. THUS, PRRS REMAINS THE MOST ECONOMICALLY SIGNIFICANT DISEASE IN THE US PORK INDUSTRY. COMMERCIAL VACCINES ARE AVAILABLE BUT THEIR SAFETY AND EFFICACY ARE LESS SATISFACTORY AND THE DISEASE CONTINUES TO DAMAGE THE US SWINE INDUSTRY. THE MAIN OBSTACLES TO CONTROLLING PRRS ARE DUE TO 1) UNUSUAL IMMUNE RESPONSE OF PIGS (HOST FACTOR), 2) ANTIGENIC VARIATION OF THE VIRUS (VIRAL FACTOR), AND COINFECTION WITH BACTERIAL PATHOGENS ON FARMS (ENVIRONMENTAL FACTOR). THE CURRENT PROJECT WILL ADDRESS ALL THREE FACTORS.THE SURVIVAL OF PRRS VIRUS IN PIGS REQUIRES THE BALANCE BETWEEN REPLICATION OF VIRUS AND ANTIVIRAL DEFENSE OF HOST. THE ANTIVIRAL DEFENSE CONSISTS OF A VARIETY OF IMMUNE SURVEILLANCE SYSTEMS TO ELIMINATE INVADING VIRUSES, AND IN TURN, PRRS VIRUS HAS EVOLVED TO AVOID THESE IMMUNE BARRIERS. THE IMMUNOLOGICAL HALLMARKS IN PRRS VIRUS-INFECTED PIGS INCLUDE THE SUPPRESSION OF TYPE I INTERERON (IFN) RESPONSE AND THE DELAYED AND POOR ADAPTIVE IMMUNITY. TYPE I IFNS ARE THE MOST POTENT ANTIVIRAL CYTOKINE AND TRIGGER ADAPTIVE IMMUNE RESPONSES, AND THUS SUPPRESSION OF TYPE I IFNS NEGATIVELY AFFECTS BOTH INNATE AND ADAPTIVE IMMUNITIES OF PIGS. ON FARMS, BACTERIAL PATHOGENS ARE COMMON, AND PIGS PREDISPOSED BY PRRS TEND TO DEVELOP CLINICALLY MORE SEVERE DISEASE WHEN CO-INFECTED WITH A BACTERIAL PATHOGEN THAN PRRS ALONE. A SYNERGISTIC PRODUCTION OF PROINFLAMMATORY CYTOKINES IS EVIDENT IN PIGS COINFECTED WITH PRRS VIRUS AND A BACTERIAL PATHOGEN, AND IT IS DUE TO THE POSITIVE FEEDBACK OF CYTOKINES PRODUCED BY PRRSV.THIS PROJECT WILL ENHANCE THE HOST IMMUNE RESPONSE OF PIGS AND REDUCE CLINICAL SEVERITY DURING COINFECTION OF PRRS VIRUS AND BACTERIAL PATHOGENS ON FARMS. THE STUDY TARGETS TWO VIRAL PROTEINS (NSP1Β AND N) TO ACHIEVE THESE GOALS.NSP1Β PROTEIN IS A POTENT IFN SUPPRESSOR, AND WE WILL REMOVE THE IFN SUPPRESSION FUNCTION FROM PRRS VIRUS TO GENERATE IFN SUPPRESSION-NEGATIVE VIRUS.N PROTEIN ACTIVATES NF-KB AND THUS STIMULATES PROINFLAMMATORY CYTOKINE PRODUCTIONS. WE WILL REMOVE THE NF-KB ACTIVATION FUNCTION FROM PRRSV TO GENERATE NF-ΚB ACTIVATION-NEGATIVE VIRUS.A DOUBLE-DELETION MUTANT PRRS VIRUS WILL BE GENERATED WHICH WILL BE IFN-SUPPRESSION-NEGATIVE AND PROINFLAMMATORY CYTOKINE ACTIVATION-NEGATIVE.IMMUNIZATION OF PIGS WITH THIS VIRUS WILL RESULT IN IMPROVED IMMUNE RESPONSE AND REDUCTION OF CLINICAL SEVERITY DURING COINFECTION WITH A BACTERIAL PATHOGEN. THIS HYPOTHESIS WILL BE EXAMINED IN PIGS.BASED ON THE FINDINGS, A NEW STRATEGY WILL BE DESIGNED FOR A BETTER VACCINE CANDIDATE. OUR STUDY ESTABLISHES A MODEL SYSTEM TO ENHANCE OUR UNDERSTANDING OF HOW TO COMBAT AN ATYPICAL VIRAL DISEASE IN FOOD ANIMALS. THIS STUDY ADDRESSES THE 2017 USDA NIFA PROGRAM AREA DESCRIPTION; PRIORITY AREA: ANIMAL HEALTH AND PRODUCTION AND ANIMAL PRODUCTS; PROGRAM AREA PRIORITY CODE: A1221 (ANIMAL HEALTH AND DISEASE).

University Of Illinois

Investigators