Inhibition of bovine immunodeficiency virus by anti-HIV-1 compounds in a cell culture-based assay.
The bovine immunodeficiency virus (BIV) and human immunodeficiency virus types 1 and 2 (HIV-1 and -2) are members of the lentivirus genus of retroviruses. Although DNA sequences of these viruses have diverged considerably, the BIV genome organization, function of structural and regulatory genes, and replication cycle are very similar to that of HIV-1, making BIV a potentially useful model to study compounds with anti-HIV-1 activity. A cell culture-based antiviral assay was developed to test compounds for inhibition of BIV replication. The assay uses an embryonic rabbit epithelial (EREp) cell line that is highly sensitive to BIV infection and cytopathology. The 50% effective concentrations (EC50) at which the virus was inhibited in EREp cells were determined for 13 nucleoside analog, non-nucleoside, tumor-suppressive, or membrane-surface inhibitory compounds. The nucleoside analogs (3'-azido-2',3'-dideoxythymidine, 2',3'-dideoxyinosine and 2',3'-dideoxycytosine), surface-membrane inhibitors (dextran sulfate, hypericin, Chicago Sky Blue and quinobene), the nucleoside reductase inhibitor (hydroxyurea), and a tumor-suppressive phorbol ester (prostratin) inhibited BIV with EC50 values similar to those derived in HIV-1 lymphocyte (CD4+)-based assays. BIV was markedly more resistant to inhibition with HIV-1-specific non-nucleoside reverse transcriptase inhibitors (NNRTIs) (thiazolobenzimidazole, oxathiin carboxanilide and thiocarbamate) than was HIV-1, which parallels results with NNRTIs in HIV-2 assays.
Tobin
G J
GJ
Laboratory of Cell and Molecular Structure, SAIC Frederick, MD, USA. tobin@mail.ncifcrf.gov
Ennis
W H
WH
Clanton
D J
DJ
Gonda
M A
MA
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000633:toxicity; D002417:Cattle; D002460:Cell Line; D015497:HIV-1; D006801:Humans; D016087:Immunodeficiency Virus, Bovine / Q000187:drug effects*; D009705:Nucleosides / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011817:Rabbits; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology
D019380:Anti-HIV Agents; D009705:Nucleosides; D010703:Phorbol Esters; D018894:Reverse Transcriptase Inhibitors; C070999:prostratin