We have during the past twenty years utilized the equine infectious anemia virus (EIAV) system as an animal model for examining fundamental aspects of lentivirus replication and mechanisms of persistence and pathogenesis. Based on these previous studies, we hypothesize that further development of the EIAV system depends on a more detailed characterization of cellular factors involved in viral replication and that knowledge of specific viral-cellular interfaces can reveal novel replication pathways that may be targeted by antiviral agents. To address these cellular and molecular biology aspects of EIAV replication, we have during the past year expanded our collaborative interdisciplinary research team to include relevant cellular biology expertise. Thus, we propose the following specific aims to characterized in detail critical aspects of EIAV infection, gene expression, and budding, respectively: (i) to characterize the cellular receptors used by EIAV in target cells in vitro and the influence of receptor specificity on tissue tropism in vivo; (ii) to determine the influence of cellular transcription factors and LTR variation on EIAV tropism and pathogenesis; (iii) to define the cellular pathways involved in EIAV assembly and budding. It is anticipated that the results of these studies will provide new insights into the fundamental aspects of how lentiviruses specifically recruit and adapt cellular processes to achieve viral replication. Thus, these studies may define new specific lentiviral-cellular interactions that may be evaluated as potential targets for antiretroviral compounds ands including the treatment of HIV-1 infection and disease.