Anti-Fas monoclonal antibody is cytocidal to human immunodeficiency virus-infected cells without augmenting viral replication
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N Kobayashi1, Y Hamamoto, N Yamamoto
1Department of Virology and Parasitology, School of Medicine, Yamaguchi University, Japan.
Insights
A novel monoclonal antibody targeting the Fas antigen selectively eliminates human immunodeficiency virus (HIV)-infected cells. This antibody inhibits viral spread without augmenting HIV replication, offering a potential therapeutic strategy.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- The Fas antigen, a cell surface receptor linked to tumor necrosis factor (TNF) signaling, plays a role in cellular apoptosis.
- Human immunodeficiency virus (HIV) infection leads to chronic immune activation and cell death.
- Understanding mechanisms to selectively eliminate HIV-infected cells is crucial for therapeutic development.
Purpose of the Study:
- To investigate the in vitro activity of a cytotoxic monoclonal antibody (anti-Fas mAb) against the Fas antigen on HIV-infected cells.
- To compare the effects of anti-Fas mAb and TNF on HIV-infected cells.
- To assess the potential of anti-Fas mAb in suppressing HIV spread and replication.
Main Methods:
- Culturing chronically HIV-infected and uninfected human cells.
- Treatment with anti-Fas mAb and/or TNF.
- Assessment of cell viability, HIV replication markers (mRNA synthesis, syncytia formation), and viral spread.
Main Results:
- Both TNF and anti-Fas mAb selectively killed chronically HIV-infected cells, with uninfected cells showing less sensitivity.
- Anti-Fas mAb suppressed the spread of HIV-infected cells when applied immediately post-infection.
- Unlike TNF, anti-Fas mAb did not augment HIV replication or enhance HIV-induced syncytia formation.
Conclusions:
- Anti-Fas mAb effectively mimics the cytocidal action of TNF against HIV-infected cells.
- Anti-Fas mAb demonstrates potential for inhibiting HIV spread without exacerbating viral replication.
- Targeting the Fas pathway with specific antibodies presents a promising avenue for controlling HIV infection.
Abstract:
A cytotoxic monoclonal antibody (anti-Fas mAb) against the 200-kDa cell surface Fas antigen, which is associated with the tumor necrosis factor (TNF) receptor, was examined for its in vitro activity on human immunodeficiency virus (HIV)-infected cells. It was found that both TNF and anti-Fas mAb selectively killed the chronically HIV-infected cells. Uninfected cells were less sensitive to the antibody than those infected with HIV. When the cells were cultured in the presence of anti-Fas mAb immediately after the HIV infection, the spread of HIV-infected cells was suppressed by the antibody. TNF augmented both the synthesis of HIV-specific mRNA in HIV-infected cells and formation of multinucleated giant cells. In contrast, the anti-Fas mAb did not augment HIV replication or enhance the HIV-induced formation of syncytia. The results indicated that anti-Fas mAb mimicks the cytocidal action of TNF but does not augment HIV replication.