J. Comp. Path. ]]]] , Vol. ] , ]]]^]]] Detection of Maedi-Visna Virus in the Liver and Heart of Naturally Infected Sheep G. D. Brellou, K. Angelopoulou * , T. Poutahidis and I. Vlemmas Laboratory of Pathology, and * Laboratory of Biochemistry andToxicology, School ofVeterinary Medicine, Aristotle University ofThessaloniki,Thessaloniki 54124, Greece Summary Maedi-visna virus (MVV) in sheep, which infects mainly cells of the monocyte/macrophage lineage, produces changes in the lung, mammary gland, brain and joints. In this study, however, the liver and heart of six naturally infected sheep were examined for the presence of the virus. MVV proviral DNAwas demonstrated by polymerase chain reaction (PCR) analysis, and immunohistochemical examination revealed viral antigens in the cytoplasm of hepatocytes and cardiac myocytes. Although histopathological examination showed mild to moderate, chronic lymphocytic cholangiohepatitis and myocarditis and the presence of small lymphoid aggregates, the typical mae- di lymphoproliferative lesions (lymphoid follicle-like structures of considerable size with germinal centres) were not seen in the liver and heart.These novel ¢ndings suggest that, although the macrophage is the main cell for productive viral replication, the liver and heart represent additional MVV targets. r 2006 Elsevier Ltd. All rights reserved. Keywords: cardiac myocytes; heart; hepatocytes; liver; maedi-visna; small ruminant lentiviruses; viral infection Introduction Ovine maedi-visna virus (MVV) and caprine arthri- tis-encephalitis virus (CAEV) are small ruminant len- tiviruses (SRLVs) that mainly infect cells of the monocyte/macrophage lineage and cause slowly pro- gressive fatal diseases in numerous countries. Replica- tion of the virus in a¡ected tissues results in a chronic lymphohistiocytic in£ammatory response, with the formation of typical lymphoid follicle-like nodules in several organs. Such lesions, which are immune- mediated, are characteristic of SRLVs (Narayan, 1990; Clements and Payne, 1994; Clements and Zink, 1996 ; Pe Ł pin et al .,1998 ). The distribution of lesions varies, but most cases show some or all of the following changes: lymphohistiocytic interstitial pneumonia, pulmonary lymphoid hyperplasia, lymphocytic indurative masti- tis, lymphocytic polyarthritis, lymphocytic encephalo- myelitis, and follicular hyperplasia in the lymph nodes and spleen (Clements and Zink,1996 ; Jones et al .,1997 ). Host factors and viral strain may contribute to the dif- ferent pathological manifestations. Indeed, viral strains with di¡erent pathogenicity and organ tropism, originating from various geographical areas, show high genomic variability (de la Concha-Bermejillo, 1997 ; Leroux et al ., 1997 ; Pe Ł pin et al ., 1998 ; Peterhans et al ., 2004 ). An essential issue in SRLV pathogenesis has always been whether cells other than macrophages can har- bour the virus and, in particular, whether these cells can support viral replication in vivo (Clements and Zink, 1996 ). The detection of viral RNA and proviral DNA in tissue sections from infected sheep and goats revealed that SRLVs could enter a broad range of cell types, such as dendritic cells, lymphocytes, plasma- cytes, endothelial cells, ¢broblasts, adipocytes, micro- glial cells and pericytes, as well as epithelial cells of the bronchi, alveoli, mammary glands, thyroid folli- cles, choroid plexus, small intestine, renal tubules and third eyelids (Georgsson et al ., 1989; Zink et al ., 1990; Staskus et al ., 1991 ; Ryan et al ., 2000; Capucchio et al ., 2003 ; Carrozza et al ., 2003 ; Preziuso et al ., 2004; Biescas www.elsevier.com/locate/jcpa ARTICLE IN PRESS 0021-9975/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi: 10.1016/j.jcpa.2006.10.001 Correspondence to: T. Poutahidis (e-mail: teoput@vet.auth.gr). Please cite this article as: G.D. Brellou, et al., Detection of Maedi-VisnaVirus in the Liver and Heart of Naturally Infected Sheep, J. Comp. Path. (2007), doi: 10.1016/j.jcpa.2006.10.001