Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses

Abstract

EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed.

Figure 1

Grading of the histological lesions from lung sections. A. Absence of histological lesion in the lung parenchyma of an EIAV^NEG horse (#91-rom). B. Mild lesions of broncho-interstitial pneumonia in an EIAV^POS horse (#1-rom) revealed peribronchiolar and interstitial lymphocytic accumulation with mild thickening of the interlobular septa. C. Moderate lesions in EIAV^POS horse (#78-fr) with accumulation of lymphocytes within the septa and moderate thickening of the alveolar walls. D. Severe lesions of interstitial pneumonia in EIAV^POS horse (# 2-rom) with peribronchiolar lymphocyte infiltration, partial destruction of bronchiolar epithelium, peribronchiolar accumulation of smooth muscle cells and thickening and partial destruction of the alveolar septal leukocyte exudate. (►) Interstitial lymphocyte accumulation; (✶) thickening of the interlobular septa; (➔) destruction of alveolar walls; () peribronchiolar accumulation of smooth muscle cells; a: alveoli; b: bronchiole.

Figure 2

Distribution of interstitial lung lesions in horses according to their EIAV status. The histological scores are reported for the EIAV^POS and EIAV^NEG populations. This score was used to sort the horses according to the severity of the observed lung pathology where 0 to 0.4 means no lesions, 0.5 to 1.4 mild lesions, 1.5 to 2.4 moderate lesions and > 2.4 severe lesions. N: number of horses.

Figure 3

Smooth muscle cell accumulation in the lung parenchyma (horse #16-rom). A. Smooth muscle cells accumulate into the lung parenchyma () and disrupt the bronchiolar structure. Hematoxylin-eosin staining on paraffin-embedded sections. B. Immunostaining of smooth muscle cells using an anti-αSMA antibody shows the accumulation of fusiform cells (in green) within the lung parenchyma. C. Higher magnification shows organized actin filaments within the infiltrating cells. Nucleus are stained in blue with DAPI.

Figure 4

Expression of EIAV p26 capsid in lung sections of EIAV^POS horses. A. Capsid expression in macrophages present in the interstitial lung tissue from an EIAV^POS horse (#5-rom); original magnification X400; B. Capsid expression in mononuclear inflammatory cells infiltrating the lung parenchyma around a blood vessel (v); horse #2-rom; original magnification X200; C. Capsid expression in epithelial cells of the alveolar walls, compatible with AECII and AECI; EIAV^POS horse #5-rom; original magnification X400; D. Capsid expression in bronchiolar epithelial cells or club cells (Clara); EIAV^POS horse #23-rom; original magnification X200; a: alveoli; b: bronchiole. Red: p26 expression (►); blue: nucleus stained with DAPI.