The horse lentivirus, equine infectious anemia virus (EIAV), is a retrovirus closely related to the human immunodeficiency virus. EIAV is useful as a model for the study of retroviral expression and latency. In addition, a simple assay has been developed using EIAV infection to screen antiviral drugs. A. The role of the Tat, or transactivator, protein in EIAV is being studied. We investigated the ability of EIAV Tat to upregulate EIAV gene expression in a number of different cell lines. Not all cell lines supported EIAV and HIV transactivation equally. All primate cell lines were unable to support EIAV transactivation, despite the ability of these cells to support high levels of HIV transactivation. Identification of the region(s) within EIAV and HIV Tat molecules responsible for the cell line specificity is currently ongoing. B. Latency and viral reactivation in an EIAV-seropositive mare is being investigated. This mare has never been clinically ill with EIAV. No infectious virus has ever been detected in her. Upon corticosteroid treatment of the mare, viral sequences were detected in monocytes isolated from the mare ten days post treatment. In vitro differentiated macrophages derived from her monocytes were treated with mitogens. These treatments resulted in significant increases in the amount of detectable viral sequences detected by PCR amplification. The upregulation of viral expression by mitogens is currently being studied. In a related project, EIAV peptide specific antisera have been raised in rabbits. These antisera are currently being characterized and will be used to identify which EIAV proteins are being made in the EIAV sero- positive horse as well as other EIAV molecular constructs. C. A viral infectivity assay has been developed that allows for relatively simple screening of potential antiviral drugs. This assay involves immunostaining of EIAV positive cells in the presence or absence of drugs in adherent cell lines. Since EIAV infects a number of different adherent cell lines from several different species, the role of the cell on the effect of antiviral drugs can be evaluated. The use of EIAV which is not infectious to humans to screen antivirals overcomes many of the biohazards involved in using HIV to identify new drugs. In collaboration with Dr. Tom North, EIAV reverse transcriptase is being purified from viral particles and drug interaction studies with the purified enzyme are under investigation.
