Maedi-Visna Virus and its Relationship to Human Immunodeficiency Virus

Maedi-visna is a slow virus infection of sheep leading to a progressing lymphoproliferative disease whichis invariably fatal. It affects multiple organs, but primarily the lungs where it causes interstitial pneumonia(maedi). Infection of the central nervous system was commonly observed in Icelandic sheep (visna), infectionof mammary glands (hard udder) in sheep in Europe and the USA, and infection of the joints insheep in the USA. The name ovine progressive pneumonia (OPP) is commonly used in the USA and ovinelentivirus (OvLV) infection is also a name used for maedi-visna. A related infection of goats, caprine arthritis-encephalitis (CAE), is common in Europe and the USA. The natural transmission of maedi-visna ismostly by the respiratory route, but also to newborn lambs by colostrum and milk. Intrauterine transmissionseems to be rare and venereal transmission is not well documented. Macrophages are the majortarget cells of maedi-visna virus (MVV), but viral replication is greatly restricted in the animal host, apparentlydue to a posttranscriptional block. The low-grade viral production in infected tissues can explainthe slow course of the disease in sheep. The lesions in maedi-visna consist of infiltrates of lymphocytes,plasma cells, and macrophages, and are detectable shortly after experimental transmission. Several studiesindicate that the lesions are immune mediated and that cytotoxic T-lymphocytes may be importanteffector cells. The persistence of the MVV infection is explained by a reservoir of latently infected bloodand bone marrow monocytes, which migrate into the target organs and mature into macrophages withproviral DNA transcription, but limited replication of virus. The MVV particles are morphologically similarto those of other retroviruses and the mode of replication follows the same general pattern. The genomeorganization and gene regulation resembles that of other lentiviruses. In addition to gag, pol and env,MVV has three auxiliary genes (tat, rev and vif), which seem to have similar functions as in other lentiviruses,with a possible exception of the tat gene. A determination of the 9200 nucleotide sequence of theMVV genome shows a close relationship to CAE virus, but limited sequence homology with other lentiviruses,and only in certain conserved domains of the reverse transcriptase and possibly in the surfaceprotein. MVV infection in sheep and HIV-1 infection in humans have a number of features in commonsuch as a long preclinical period following transmission, and a slow development of multiorgan diseasewith fatal outcome. A brief early acute phase, which is terminated by the immune response, is also aninteresting common feature. Like HIV-1, MVV is macrophage tropic and the early stages of the HIV-1 infectionwhich affect the central nervous system and the lungs are in many ways comparable to maedi-visna.In contrast to HIV-1, MVV does not infect T-lymphocytes and does not cause T-cell depletion and immunodeficiency.This is responsible for the difference in the late stages of the HIV-1 and MVV infections andthe final clinical outcome. Despite limited sequence homology, certain proteins of MVV and HIV-1 showstructural and functional similarities. Studies of MVV may therefore help in the search for new drugsagainst lentiviruses, including HIV-1.