The scene of lung pathology during PRRSV-1 infection

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important infectious diseases for the pig industry worldwide. The disease was firstly reported in 1987 and became endemic in many countries. Since then, outbreaks caused by strains of high virulence have been reported several times in Asia, America and Europe. Interstitial pneumonia, microscopically characterised by thickened alveolar septa, is the hallmark lesion of PRRS. However, suppurative bronchopneumonia and proliferative and necrotising pneumonia are also observed, particularly when a virulent strain is involved. This raises the question of whether the infection by certain strains results in an overstimulation of the proinflammatory response and whether there is some degree of correlation between the strain involved and a particular pattern of lung injury. Thus, it is of interest to know how the inflammatory response is modulated in these cases due to the interplay between virus and host factors. This review provides an overview of the macroscopic, microscopic, and molecular pathology of PRRSV-1 strains in the lung, emphasising the differences between strains of different virulence.

Keywords: PRRSV-1; bronchopneumonia; inflammation; interstitial pneumonia; lung; pathology; virulence.

Figure 1

Gross pictures of lungs from pigs experimentally infected with PRRSV-1 strains of different virulence and euthanised at 8–10 dpi. (A) Lung of a pig infected with 3249 strain showing tan mottling areas (arrowheads), and not collapsing after removal from thoracic cavity. (B) Lung from a pig infected with the highly virulent Rosalía strain displaying a marked reddish mottle pattern and diffuse firmness, especially in the dorsal aspect of the lung (arrowheads). Inset shows higher magnification and section of one of the affected lobes. Arrowheads show interstitial oedema. (C) Lung from a Lena-infected pig exhibiting tan areas and rubbery texture but also patchy ventral areas of consolidation of the cranial and middle lung lobes (arrows). Inset shows higher magnification and section of the consolidation area of one of the affected lobes.

Figure 2

Microscopic pictures of the lung of representative pigs experimentally infected with PRRSV-1 strains of different virulence and euthanised at 8–10 dpi. (A) Mild thickening of the alveolar septa because of minimal infiltration of macrophages and lymphocytes in the lung tissue of a piglet infected with 3249 strain. (B) Moderate to severe thickening of the alveolar septa due to marked infiltration of mononuclear cells with the presence of a syncytia (inset) in the lung of a Lena-infected pig. (C) Lung tissue of a Lena-infected pig showing, together with thickening of the alveolar septa, degenerated neutrophils within the lumen of bronchioles (arrowhead) and alveoli as well as cellular debris and aggregates of free chromatin (see for details “G”). (D) Moderate thickening of alveolar septa with characteristic perivascular lymphocytic and histiocytic infiltrate together with areas of moderate atelectasis in the lung of SU1-bel-infected pig. (E) Similar lesions as reported in “D” with marked infiltration of macrophages in the alveolar septa and atelectasis in the lung of a pig infected with Rosalía strain. See “F” for detail of the periarteriolar infiltrate.

Figure 3

Microscopic pictures of representative score of interstitial pneumonia in PRRSV-1 infected pigs. (A) Score 1, mild interstitial pneumonia. Mild thickening of the alveolar septa because of minimal infiltration of macrophages and lymphocytes in the lung tissue of a piglet infected with 3249 strain. (B) Score 2, moderate interstitial pneumonia. Thickening of the alveolar walls due to moderate infiltration of macrophages and lymphocytes in the lung tissue of a piglet infected with the virulent Lena strain. (C) Score 3, moderate diffuse interstitial pneumonia. Infiltration of macrophages and scattered lymphocytes in the lung tissue of a piglet infected with the virulent Lena strain. (D) Score 4, severe diffuse interstitial pneumonia in the lung tissue of a piglet infected with the virulent Lena strain.

Figure 4

Microscopic pictures of representative score of suppurative bronchopneumonia in PRRSV-1 infected pigs. (A) Score 1, mild bronchopneumonia in the lung from 3249 infected animal. Granulocytes and macrophages are present in the alveolar septa. (B) Score 2, moderate multifocal bronchopneumonia in the lung from an animal infected with the virulent Lena strain. A high number of granulocytes (arrowheads) and macrophages, together with cell debris infiltrate the alveolar walls. (C) Score 3, moderate diffuse bronchopneumonia in the lung from an animal infected with Lena strain. Granulocytes (arrowheads), macrophages, and cellular debris within the lumen of bronchi, bronchioles (arrow), and alveoli. Inset show infiltration of macrophages and scattered lymphocytes and granulocytes. (D) Score 4, severe bronchopneumonia in the lung from an animal infected with Lena strain. Arrowheads and inset show infiltration of granulocytes within bronchioli and alveoli, respectively.

Figure 5

Microscopic pictures of the lung of representative pigs experimentally infected with the virulent Lena strain euthanised at 8 dpi (A) and with the highly virulent Rosalía strain and euthanised at 10 (B,C) and 35 dpi (D). (A) Thickening of the pleura due to the presence of fibrin (fibrinous pleuritis). (B) Alveolar septa are thickened by macrophages and lymphocytes which also predominantly infiltrate the interlobular septa (arrowheads). (C) The lung is moderately atelectatic, with type II pneumocytes hyperplasia and alveoli filling in by necrotic cellular debris (arrowheads), including basophilic clumps of chromatin, compatible with proliferative and necrotising areas of pneumonia. (D) Subpleural well-demarcated accumulation of lymphocytes consistent with a tertiary lymphoid organ.

Figure 6

Microscopic pictures of clumps of free chromatin demonstrated using Feulgen staining (A), TUNEL (B) and cleaved-caspase-3 (C) immunohistochemical staining in the lung tissue from virulent Lena infected animals with severe bronchopneumonia. (A) Feulgen⁺ staining which demonstrates the presence of clumps of free chromatin. (B) TUNEL and (C) cleaved-caspase-3 stainings showing the negativity of the clumps of free chromatin.

Figure 7

Microscopic pictures of PRRSV-N-protein immunohistochemical staining in lung tissue from virulent Lena infected animals euthanised at 8 dpi. (A) PRRSV-N-protein⁺ alveolar macrophages in a field of representative interstitial pneumonia. Inset shows higher magnification of PRRSV-N-protein⁺ alveolar macrophages. (B) Clusters of PRRSV-N-protein⁺ macrophages surrounded by apoptotic bodies.

Figure 8

Graphic representation of pulmonary lesions induced by PRRSV-1 strains of different virulence (created with BioRender.com). PRRSV-1 classical strains (moderately virulent) typically induce a low to moderate interstitial pneumonia. In contrast, virulent PRRSV-1 strains exhibit heightened viral replication, leading to a significant reduction in pulmonary alveolar macrophages (PAMs) accompanied by early cell death of infected PAMs. Additionally, these strains trigger necrosis and apoptosis in other macrophages and lymphocytes, resulting not only in severe interstitial pneumonia but also, in some instances, in bronchitis, bronchiolitis, and bronchopneumonia. These alterations contribute to an imbalance in pulmonary immune homeostasis, making the host more susceptible to a wide spectrum of respiratory pathogens. The immunopathogenesis of these lesions is partly attributed to a stronger inflammatory response mediated by IL-1α/β when compared to low to moderately virulent strains.