Pathogenesis of porcine reproductive and respiratory syndrome virus-induced increase in susceptibility to Streptococcus suis infection.

Eighty 3-week-old crossbred pigs were randomly assigned to six groups (13-14 pigs/group). Group 1 pigs served as uninoculated controls, group 2 pigs were inoculated intranasally (i.n.) with Streptococcus suis serotype 2, group 3 pigs were inoculated i.n. with a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine, group 4 pigs were inoculated i.n. with the same vaccine and with S. suis, group 5 pigs were inoculated i.n. with VR-2385 (a high-virulence strain of PRRSV), and group 6 pigs were inoculated i.n. with VR-2385 and S. suis. Pigs exposed to both PRRSV and S. suis were inoculated with PRRSV 7 days prior to S. suis inoculation. The pigs were 26 days old when inoculated with S. suis. Respiratory disease was significantly more severe in groups 5 and 6. Mortality rate was the highest in group 6 (87.5%). This rate was significantly higher than that observed in all other groups except group 4 (37.5%). The mortality rate in group 2, inoculated with S. suis alone, was 14.3%. No pigs from groups 1, 3, or 5 died prior to the scheduled necropsies at 10 and 28 days postinoculation with PRRSV (DPI). To study the effect of PRRSV and/or S. suis on pulmonary clearance by pulmonary intravascular macrophages, six pigs from each group were intravenously infused with 3% copper phthalocyanine tetrasulfonic acid in saline prior to necropsy at 10 DPI. Mean copper levels in the lungs of pigs in groups 2, 5, and 6 were significantly lower than those in control pigs. The mean percentage of lung tissue grossly affected by pneumonia at 10 DPI was 0%, 1%, 0%, 3%, 64%, and 62% for groups 1-6, respectively. Both gross and microscopic interstitial pneumonia lesions were significantly more severe in the VR2385-inoculated groups (5 and 6). PRRSV was isolated from bronchoalveolar lavage fluid collected at necropsy from 100% of the pigs in groups 5 and 6, 71.4% of pigs in group 4, 38.5% of pigs in group 3, and none of the pigs in groups 1 or 2. Streptococcus suis serotype 2 was cultured from the internal tissues of 7.7%, 28.6%, and 78.6% of the pigs in groups 2, 4, and 6, respectively. Streptococcus suis serotype 2 was isolated from whole blood at necropsy from 7.7%, 35.7%, and 78.6% of pigs in groups 2, 4, and 6, respectively. Significantly more pigs in group 6 had S. suis isolated from whole blood and internal tissues. In summary, both high-virulence PRRSV and S. suis decreased copper clearance, and the incidence of isolation of S. suis and PRRSV was higher in dually inoculated pigs. PRRSV-induced suppression of pulmonary intravascular macrophage function may in part explain PRRSV-associated increased susceptibility to S. suis infection.

Effects of low (modified-live virus vaccine) and high (VR-2385)-virulence strains of porcine reproductive and respiratory syndrome virus on pulmonary clearance of copper particles in pigs.

Seventy-five 3-week-old, crossbred pigs from a herd free of porcine reproductive and respiratory syndrome virus (PRSSV) were randomly assigned to three groups: uninfected controls, pigs inoculated intranasally with RespPRRS/Repro modified-live virus vaccine (RespPRRS), and pigs inoculated intranasally with a high-virulence strain of PRRSV (VR-2385). Pigs were intravenously infused with 3% copper phthalocyanine tetrasulfonic acid (0.2 ml/kg) in normal saline 30 minutes before necropsy, which was performed 3, 7, 10, 14, or 28 days postinoculation (DPI) with PRRSV. There were no differences in serum copper concentration in samples collected at 0, 15, or 30 minutes after infusion. Copper concentrations in the lungs of VR-2385-inoculated pigs were significantly lower than levels in the lungs of control and RespPRRS-inoculated pigs at 7, 10, and 14 DPI (P < 0.05). The greatest difference between the groups was observed at 10 DPI. Liver and spleen copper concentrations were slightly, but not significantly, higher in both PRRSV-infected groups. The percentage of lung affected by grossly visible pneumonia ranged from 0 to 5.6% in the RespPRRS-inoculated group and from 15.2 to 46.4% in the VR-2385-inoculated group, with lesions peaking at 7 and 10 DPI, respectively. PRRSV antigen was demonstrated in both pulmonary alveolar macrophages (PAMs) and pulmonary intravascular macrophages (PIMs) by immunohistochemical methods. Copper particles were demonstrated in the PIMs by light microscopy. PRRSV was isolated from bronchoalveolar lavage fluid of VR-2385-infected pigs from 3 to 28 DPI and from RespPRRS-inoculated pigs from 7 to 28 DPI. No PRRSV, PRRSV antibodies, or PRRSV-induced pneumonia was detected in the control group. These results suggest that 1) PRRSV has a detrimental effect on the uptake of copper particles by PIMs, 2) the severity of PRRSV-induced damage to PIMs differs among strains, and 3) demonstration of PRRSV-induced decreased pulmonary clearance supports the hypothesis that PRRSV infection may make pigs more susceptible to bacterial septicemia.

Experimental infection of pigs with the newly identified swine hepatitis E virus (swine HEV), but not with human strains of HEV.

A novel virus of pigs, swine hepatitis E virus (swine HEV), was recently identified and shown to be antigenically and genetically related to human HEV. In the present study, we attempted to infect specific-pathogen-free (SPF) pigs experimentally with swine HEV or with human strains of HEV. Serum samples collected from naturally infected pigs were used as the source of swine HEV. Pigs inoculated intravenously with serum samples containing swine HEV seroconverted to anti-HEV 4 to 8 weeks postinoculation, and the virus spread to an uninoculated pig. Swine HEV was detected in nasal and rectal swab materials as early as 2 weeks postinoculation and for 4 to 8 weeks thereafter. Viremia appeared 4 to 6 weeks postinoculation and lasted 1 to 3 weeks. The inoculated pigs appeared clinically normal and serum liver enzymes were not significantly elevated. In contrast, pigs were not infected when inoculated intravenously with about 10(5) monkey infectious doses of one of two human strains of HEV (Sar-55 or Mex-14).