Interferon-gamma: A Potent Antiviral Agent Targeting Macrophages Infected with LP-BM5 Murine Leukemia Virus, the Causative Agent of 'AIDS' in Mice

Cells of the monocyte/macrophage lineage (MM cells) are known to beinfected by retroviruses, including the human immunodeficiency virus (HIV), without cytopathic changesand may serve as a persistent reservoir for the virus during the development of immunodeficiency disease.LP-BM5 murine leukemia virus (MuLV) infection of C57BL/6 mice and cell lines has been used to optimizetherapy directed against macrophages. Findings in this murine system may be applicable to HN infectionin humans. The effect of recombinant murine interferon-gamma (IFN-γ) and 3' -azido-2',3' -dideoxythymidine(AZT) as single agents or in combination was investigated in both LP-BM5 MuLV de novo infection andchronic infection of macrophages. Results indicate that the therapeutic effects of these single agents weredose-dependent and both agents were similarly effective in reducing the production of infectious virusdetermined by XC-plaque assay and by measurements of reverse transcriptase activity in culture supernatants;and AZT and IFN-γ reduced the production of virus proteins, quantified by laser densitometry offluorographs from immunoprecipitated viral proteins using virus-specific antiserum. A combination of IFN-γand that AZT showed greater antiviral activity in both LP-BM5 MuLV de novo and chronic infection ofmacrophages than either agent alone, suggesting that IFN-γ and AZT represent a potent combination ofantiviral agents targeting macrophages. Further, since a lower concentration of each agent was requiredfor efficacy in combination therapy, toxicity associated with single agent therapy may be avoided