Interaction of Porcine Reproductive and Respiratory Syndrome virus and Porcine Circovirus type 2

Abstract

Porcine reproductive and respiratory syndrome (PRRS) has been recognized as one of the most economically important diseases in the swine industry, causing both reproductive failure in pregnant sows (late-term abortions and stillbirths) and respiratory disease (pneumonia) in nursing, growing, and finishing pigs. Because porcine reproductive and respiratory syndrome virus (PRRSV) has emerged from European countries, the virus is composed of 2 genotypes: Type 1 (European genotype) and Type 2 (North American genotype). The two PRRSV genotypes produce the same disease symptoms, but the severity is very different and there is poor protection against cross-infection in pigs. Otherwise, porcine circovirus associated disease (PCVAD) has been recognized as one of the most severe swine wasting diseases. From the first report to the current date, two types of porcine circovirus (PCV) have been recognized in the swine industry: the non-pathogenic PCV type 1 (PCV1) and the pathogenic PCV type 2 (PCV2). PCV2 is the causative agent of PCVAD. Phylogenetic analyses have shown that PCV2 isolates can be further divided into two main clusters, now commonly referred to as PCV2a and PCV2b. Actually, from the perspective of virulence, PCV2a and PCV2b are not different. But epidemiological studies indicate that PCV2b is currently the most prevalent in naturally occurring infections. Many articles have reported a PCV2-specific character in co-infection with other pathogens. The viral load and replication in tissue of co-infected pig is much higher than in a single infection. There are the many types of co-infecting pathogens that enhance PCV2 replication, such as porcine parvovirus, swine influenza virus, Mycoplasma hyopneumoniae, and Torque teno sus virus (TTSuV). However, PRRSV is the most important co-infecting pathogen because of its clinical and pathological specificity, which can make the severity of clinical signs worse and directly affect PCV2 replication. The exact mechanisms of how PRRSV co-infection with PCV2 potentiates clinical signs are unknown. Moreover, vaccine efficacy against PRRSV or PCV2 during co-infections has not been evaluated. Because PRRSV and PCV2 are prevalent in swine farms worldwide, these topics are very important. The goal of this thesis was to investigate how PRRSV or PCV2 genotypes influence each other regarding viral replication during co-infection and to determine which vaccine against PRRSV or PCV2 protects against clinical symptoms during co-infection. An experimental challenge study with a combination of PCV2a (or 2b) and type 1 (or type 2) PRRSV was performed to compare the virulence of a combination of concurrent infections in terms of PCV2 viremia and PCV2-associated lesions and antigens in co-infected pigs. Pigs challenged with PCV2a (or 2b) and type 1 (or type 2) PRRSV had significantly (P < 0.05) higher mean clinical respiratory scores and lower average daily weight gain compared with pigs with PCV2a (or 2b). Co-infection induced significantly lower levels of anti-PCV2 and anti-PRRSV IgG antibodies than infection with one genotype alone, regardless of the genotype of the two viruses. Pigs challenged with PCV2a (or 2b) and type 2 PRRSV had significantly (P < 0.05) higher levels of PCV2 viremia, more severe PCV2-associated lesions, and more PCV2 DNA within the lesions compared to pigs with PCV2a (or 2b)/type 1 PRRSV. However, there was no significant difference in these parameters in pigs with PCV2a/type 2 PRRSV or PCV2b/type 2 PRRSV. The results of this study demonstrated that there was a significant difference in the severity of PCVAD, and the difference resulted not from PCV 2 genotypes but from PRRSV genotypes. A study for the comparison of PCV2 vaccine and PRRSV vaccine efficacy was performed to determine the effects of PCV2 and PRRSV vaccinations on post-weaning multisystemic wasting syndrome (PMWS) by experimental PCV2-PRRSV challenge. A total of 72 pigs were randomly divided into 9 groups (8 pigs per group): 5 vaccinated and challenged groups, 3 non-vaccinated and challenged groups, and a negative control group. Vaccination against PCV2 induced immunological responses (NAs and PCV2-specific IFN-γ-SCs) and reduced PCV2 viremia, PCV2-induced lesions, and PCV2-antigens in the co-infected pigs. However, vaccination against PCV2 did not affect the immunological responses (NAs and PRRSV-specific IFN-γ-SCs) or, PRRSV viremia, PRRSV-induced lesions, or PRRSV antigens in the co-infected pigs. Vaccination against PRRSV did not induce immunological responses (PRRSV-specific IFN-γ-SCs) or reduce PRRSV viremia, PRRSV-induced lesions, or PRRSV antigen in the co- infected pigs. In addition, vaccination against PRRSV increased PCV2 viremia, PCV2-induced lesions, and PCV2-antigens in the co-infected pigs. In summary, vaccination against PCV2 reduced PCV2 viremia, PCV2-induced lesions, and PCV2-antigens in the dual infected pigs. However, vaccination against PRRSV increased PCV2 viremia, PCV2-induced lesions, and PCV2-antigens in the co-infected pigs. Therefore, the PCV2 vaccine decreased the potentiation of PCV2-induced lesions by PRRSV in co-infected pigs. In contrast, the PRRSV vaccine alone did not decrease the potentiation of PCV2-induced lesions by PRRSV in co-infected pigs. A study of commercial PCV2 vaccine efficacy on pigs experimentally challenged with PCV2 and PRRSV at 17 weeks post vaccination was performed to determine the effects of PCV2 vaccinations on porcine respiratory disease complex (PRDC) in Korean field conditions. A total of 60 pigs were randomly divided into 6 groups (10 pigs per group): 4 vaccinated and challenged groups, a non-vaccinated and challenged group, and a negative control group. Regardless of which commercial PCV2 vaccine was used, vaccination of piglets at 3 weeks of age was efficacious against co-challenge of PCV2 and PRRSV based on growth performance and PCV2-associated lesions. However, the inactivated chimeric PCV2 1-2 and PCV2 vaccine induced higher PCV2-specific neutralizing antibody titers and PCV2-specific interferon-γ-secreting cells and lower PCV2 viremia compared to the two PCV2 subunit vaccines. PCV2 vaccination of piglets at 3 weeks of age was effective in reducing PCV2 viremia and PCV2-associated lesions during the finishing period, which is an age frequently affected by PRDC caused by co-infection with PCV2 and PRRSV in Korean field conditions.