INHIBITION OF BOVINE IMMUNODEFICIENCY VIRUS BY ANTI-HIV-1 COMPOUNDS IN A CELL CULTURE-BASED ASSAY

The bovine immunodeficiency virus (BIV) and human immunodeficiency vir us types 1 and 2 (HIV-1 and -2) are members of the lentivirus genus of retroviruses. Although DNA sequences of these viruses have diverged c onsiderably, the BIV genome organization, function of structural and r egulatory genes, and replication cycle are very similar to that of HIV -1, making BIV a potentially useful model to study compounds with anti -HIV-l activity. A cell culture-based antiviral assay was developed to test compounds for inhibition of BIV replication. The assay uses an e mbryonic rabbit epithelial (EREp) cell line that is highly sensitive t o BIV infection and cytopathology. The 50% effective concentrations (E C(50)) at which the virus was inhibited in EREp cells were determined for 13 nucleoside analog, non-nucleoside, tumor-suppressive, or membra ne-surface inhibitory compounds. The nucleoside analogs (3'-azido-2',3 '-dideoxythymidine, 2',3'-dideoxyinosine and 2',3'-dideoxycytosine), s urface-membrane inhibitors (dextran sulfate, hypericin, Chicago Sky Bl ue and quinobene), the nucleoside reductase inhibitor (hydroxyurea), a nd a tumor-suppressive phorbol ester (prostratin) inhibited BIV with E C(50) values similar to those derived in HIV-1 lymphocyte (CD4(+))-bas ed assays. BIV was markedly more resistant to inhibition with HIV-I-sp ecific non-nucleoside reverse transcriptase inhibitors (NNRTIs) (thiaz olobenzimidazole, oxathiin carboxanilide and thiocarbamate) than was H IV-1, which parallels results with NNRTIs in HIV-2 assays.