Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections

Abstract

The innate immune response is critical for host defence against respiratory coronaviruses (CoVs). This study demonstrated that an ongoing respiratory virus infection compromises innate immune responses and affects the pathogenesis of a respiratory CoV co-infection. An innate immunosuppressive respiratory virus infection was established by infecting weaned pigs with porcine reproductive and respiratory syndrome virus (PRRSV); 10 days later, the pigs were exposed to porcine respiratory coronavirus (PRCV). The PRRSV/PRCV dual-infected pigs had reduced weight gains, a higher incidence of fever and more severe pneumonia compared with either single infection. Significant suppression of innate immune responses [reduced alpha interferon (IFN-a) levels in the lungs and reduced blood natural killer cell cytotoxicity] by the ongoing PRRSV infection was observed in dual-infected pigs, which coincided with exacerbated pneumonia during early PRCV infection. The subsequent PRCV infection led to enhanced PRRSV replication in the lungs and a trend towards increased serum T-helper type 1 (Th1) (IFN-c) but decreased Th2 [interleukin (IL)-4] responses, further exacerbating PRRSV pneumonia. Following PRCV infection, more severe PRRSV-related pulmonary alveolar macrophage (PAM) apoptosis occurred, as determined by an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay, suggesting increased PRRSV replication in PAMs. Collectively, these observations suggest interactive effects between PRCV and PRRSV via early innate (IFN-a) and later adaptive Th1 (IFN-c) and Th2 (IL-4) immune responses. These findings imply that an existing immunomodulating respiratory viral co-infection may be a contributing factor to more severe pneumonia in respiratory CoV disease. This study provides new insights into host-pathogen interactions related to co-infection by CoVs and other respiratory viruses.

Intranasal Delivery of an Adjuvanted Modified Live Porcine Reproductive and Respiratory Syndrome Virus Vaccine Reduces ROS Production

“…In contrast, unvaccinated PRRSV-challenged pig lungs had significantly increased gross lung consolidation (31). Pathological changes in the lungs of PRRSV-infected pigs are due to necrosis of virus-infected and bystander cells mediated by aberrant host immune responses (5,32,33). In the lungs of PRRSV-infected pigs, viral replication, generation of mutagenic viral quasispecies, and the cytokine storm caused by excess secretion of proinflammatory cytokines, result in ROS-mediated oxidative stress and lung pathology (5,6,34).…”

Antiviral effect of dietary germanium biotite supplementation in pigs experimentally infected with porcine reproductive and respiratory syndrome virus

“…PRRSV inhibits the production of key cytokines, such as interferon (IFN)-α [2,3], and may induce the expression of regulatory cytokines including interleukin (IL)-10 [20]. Moreover, the appearance of neutralizing antibodies is delayed in pigs infected with PRRSV [4,16,23] and these animals are more prone to develop concomitant infectious diseases [10,19]. Data from these and other studies indicate that PRRSV causes immunosuppression in the affected pigs [5,15].…”

Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

“…Tissue sections of lungs were stained with hematoxylin and eosin and examined microscopically for bronchiolar epithelial changes and peribronchiolar inflammation as described previously (24,38). Lesion severity was scored by the distribution or by the extent of lesions within the sections examined, as follows: 0, no visible changes; 1, mild focal or multifocal change, minimally different from the normal; 2, moderate multifocal change; and 3, severe and diffusely distributed change.…”

“…Lung lysates from all the euthanized pigs were prepared as described previously (3, 36) and frozen at Ϫ20°C until cytokine analysis by enzyme-linked immunosorbent assay (ELISA). Lung lysates were analyzed for innate (IFN-␣), proinflammatory (IL-6), Th2 (IL-4), Th1 (IFN-␥ and IL-12), and anti-inflammatory/T-regulatory (IL-10 and transforming growth factor ␤ [TGF-␤]) cytokines by ELISA as described previously (1,24,36).…”

“…Grossly evident pulmonary changes were assigned a score based upon the percentage of virus-affected lesions (purple-red consolidation, typical of SwIV) in each lung lobe. A total percent involvement for each lung was calculated based on weighted proportions of each lobe to the total lung volume as described previously (19,24).…”