Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV)

Abstract

In three successive experiments, the immune functions of pigs persistently infected with the porcine reproductive and respiratory syndrome virus (PRRSV) have been evaluated. Non-specific immune responses were analyzed over a period of 12 weeks post-infection (PI). In addition, the capacity of PRRSV-infected pigs to develop an efficient immune response against pseudorabies virus (PRV) glycoproteins and to resist to a subsequent virulent challenge was investigated. Our results demonstrate that PRRSV produced minor effects on the immune system of pigs. The skin delayed type hypersensitivity (DTH) in response to phytohemagglutinine injection was slightly diminished one week after challenge, but was restored thereafter. However, three weeks after the infection, the total white blood cell count, and the number of CD2+, CD8+ and IgM+ cells were enhanced. The increase in numbers of CD8+ cells persisted for three consecutive weeks. Serum immunoglobulins in infected pigs also increased by week 3 PI and up to 8 weeks PI. These results show that PRRSV may have stimulating effects on the pig immune system during the phase of long-lasting infection. After immunization with PRV glycoproteins, the production of anti-PRV antibodies and skin DTH response against PRV glycoproteins were not affected. On the contrary, following a virulent PRV challenge, PRRSV-infected pigs developed a better secondary antibody response and their resistance to the infection was as effective as in control pigs. Taken together, our data do not support a systemic immunosuppressive effect of PRRSV, during the persistent phase of infection. Other mechanisms may therefore apply to explain the emergence of secondary infections in endemically infected herds.

Fig. 1

Detection of PRRSV in the sera of infected pigs at different weeks post-infection. Histogram bars represent the percentage of viraemic pigs and vertical numbers give the corresponding mean PRRSV titres for groups 6 and 8. Titres are expressed in TCID 50 ml±standard deviations. Viraemia persisted up to 5 or 6 weeks post-infection. After PRV infection, PRRSV viraemia was not re-activated.

Fig. 2

Immunoglobulin concentration in the sera of pigs from experiment 2. Results are presented in average concentrations in mg/ml (histogram bars) and standard deviations (upper lines). Different letters indicate significative differences between groups (p<0.05). Serum immunoglobulins were titrated at different weeks after PRRSV challenge in group 6 (group 5=control group). Pigs from groups 5 and 6 were immunized with PRV glycoproteins at week 2. By 3 weeks post-infection, immunoglobulin concentration became higher in group 6 compared to group 5. All pigs included in this experiment were challenged with PRV at week 9 (group 4=control of PRV challenge). In all groups, an increase in serum immunoglobulin concentration was observed after PRV challenge. This increase was even higher in the pigs of group 4 which were not pre-immunized against PRV.

Fig. 3

Titration of anti-PRRSV antibodies by the immunoperoxydase assay (IPMA) or the seroneutralization test in absence (SNT) or in presence (SNT+COMP) of serum complement. Results are presented in average log titres (histogram bars) and standard deviations (upper lines). All pigs were challenged at week 0, then, 2 weeks later, immunized with PRV glycoproteins. At week 9, they were challenged with PRV. At weeks 0 and 1 after PRRSV infection, antibodies were not detectable by IPMA (the detection threshold for this test was 3.22 log titre). Thereafter, the log titre increased to a maximum of 9. In contrast, neutralizing antibodies were detectable to low titres by 2 or 3 weeks post-infection.

Fig. 4

Titration of PRV-neutralizing antibodies. Results are presented in average log titres (histogram bars) and standard deviations (upper lines). Different letters indicate significative differences between groups (p<0.05). Pigs from groups 3 and 6, were infected with PRRSV at week 0 (groups 2 and 5=control groups). All pigs were immunized with PRV glycoproteins at week 2, leading to a primary antibody response in conventional pigs (groups 5 and 6). In contrast, antibodies were not detectable in SPF pigs (groups 2 and 3). After PRV challenge (at week 9), a clear secondary antibody response arose in groups 5 and 6 whereas antibodies became detectable in the other groups. Differences in neutralizing antibody titres between PRRSV-infected and control pigs were observed at week 10 and 11.

Fig. 5

PRV excretion in nasal swabs. Results are presented in average log TCID 50/mg mucus (histogram bars) and standard deviations (upper lines). Different letters indicate significative differences between groups (p<0.05). In group 4, PRV excretion extended for 10 days after infection: the pigs were not immunized with PRV glycoproteins before the challenge. In contrast, PRV excretion lasted for 6 days in pigs from groups 5 and 6, which were immunized with PRV glycoproteins 7 weeks before the challenge. No differences in the level and duration of PRV excretion were seen between PRRSV-infected and control pigs.