HOST IMMUNOGENETICS PREDICT CLINICAL DISEASES IN OVINE PROGRESSIVE PNEUMONIA VIRUS INFECTED SHEEP
Location: Animal Diseases Research
Title: Ovine Progressive Pneumonia Virus Capsid Antigen as Found in CD163- and CD172a-Positive Alveolar Macrophages of Persistently Infected Sheep
Submitted to: Veterinary Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 5, 2009
Publication Date: April 9, 2010
Citation: Hoesing, L.M., Noh, S.M., Snekvik, K.R., White, S.N., Schneider, D.A., Truscott, T.C., Knowles Jr, D.P. 2010. Ovine Progressive Pneumonia Virus Capsid Antigen as Found in CD163- and CD172a-Positive Alveolar Macrophages of Persistently Infected Sheep. Veterinary Pathology. 47(3):518-528.
Interpretive Summary: Studies were initiated to evaluate the lung, mammary gland, carpal synovial membrane and brain tissues of sheep for the presence of ovine progressive pneumonia virus (OPPV) using enzyme-based immunohistochemistry (IHC) analyses. Using single enzyme-based IHC analyses, OPPV was detected in lung (n=3), mammary gland (n=3), and carpal synovial membranes (n=1), but was not detected in the choroid plexus of ten persistently infected ewes. OPPV was only found in tissues that had moderate to severe histological lesions. Using dual enzyme-based IHC analyses, it was also found that alveolar macrophages in the lung and mammary gland tissues that harbor OPPV, were also were positive for CD163 or CD172a. The observation that CD163, an anti-inflammatory phenotype, and CD172a, a down-regulatory phenotype, are found on OPPV positive alveolar macrophages suggests that persistently OPPV infected alveolar macrophages are trying to limit inflammation and activation. This study provides new insight into the mechanisms of OPPV persistence and host control of inflammation during a natural lentiviral infection.
In situ detection of ovine progressive pneumonia virus (OPPV) and the phenotypic identification of the cells which harbor OPPV have not been described for the OPPV affected tissues which include lung, mammary gland, synovial membranes of the carpal joint, and choroid plexus of the brain. In this study, we first developed a single enzyme-based automated immunohistochemical (IHC) analyses for detection of OPPV capsid (CA) using two anti-CAEV CA monoclonal antibodies, 5A1 and 10A1, and two different enzyme-based IHC systems on OPPV affected tissues. Out of ten naturally and persistently OPPV infected ewes, OPPV CA was detected in intercellular regions of the carpal synovial membrane of one ewe, in cells resembling alveolar macrophages (AMs) and pulmonary interstitial macrophages (PIMs) in lung tissue of three ewes, and in mammary alveolar cells of one ewe. OPPV CA was detected in a total of four OPPV infected sheep and was not detected in the choroid plexus in any of the OPPV infected ewes. Furthermore, dual enzyme-based automated IHC analyses revealed that OPPV CA was predominantly detected in CD172a or CD163 positive alveolar macrophages of the lungs and mammary gland. The fact that an anti-inflammatory (CD163) and downregulatory (CD172a) type of alveolar macrophage harbor OPPV CA leads to the possibility that during persistent infection with OPPV, the host alveolar macrophage serves to limit inflammation while OPPV persists undetected by the host adaptive immune response in the lung and mammary gland.