Ovine lentivirus-infected macrophages mediate productive infection in celltypes that are not susceptible to infection with cell-free virus

Ovine lentiviruses and caprine arthritis-encephalitis virus (CAEV) are prot otypic lentiviruses that replicate predominantly in macrophages of infected animals. In situ hybridization of pathologically affected tissues from dis eased animals has shown that viral RNA exists in permissive macrophages as well as in non-macrophage cell types that do not support productive virus r eplication. These findings raise questions about the cellular tropism of th ese viruses in vivo and how this may relate to their pathogenesis and the e stablishment of persistent infections. In this study, the susceptibility of macrophages and fibro-epithelial cells derived from goat synovial membrane (GSM) to infection by 14 North American ovine lentivirus strains was exami ned. All 14 strains were macrophage-tropic, as indicated by expression of v iral proteins and by fusion and development of syncytial cytopathic effects following co-culture of infected macrophages with GSM cells. In contrast, neither viral DNA nor viral proteins was detected in GSM cells inoculated w ith cell-free virus from nine of the 14 strains. Specific virus proteins we re immunoprecipitated from restrictive GSM cells following culture with inf ected macrophages and serial passage of GSM cells to remove the macrophages . The lack of infection of GSM cells by cell-free virus from some ovine len tivirus field strains was circumvented by cell-associated virus infection f rom infected macrophages to GSM cells following cell-to-cell contact. This strategy could be one of the mechanisms involved in the escape from immune surveillance and establishment of persistent infection in infected animals.