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Updated: Jun 4, 2026

Establishment and Quantification of De Novo Lytic Infection by Cell-free Kaposi's Sarcoma-Associated Herpesvirus
Published on: August 15, 2025
Inhibition of lytic reactivation of Kaposi's sarcoma-associated herpesvirus by alloferon
Naeun Lee1, Seyeon Bae, Hyemin Kim
1Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Background:
Alloferon, an immunomodulatory peptide, has antiviral capability against herpesvirus. In this research, we aimed to investigate the effect of alloferon on the regulation of the life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV), and its mechanisms. We also assessed the antiviral activity of alloferon on natural killer (NK) cells as an early antiviral immune responder.
Methods:
We first examined the change in cell proliferation and the expression of the viral genes in a KSHV-infected cell line, body-cavity-based B lymphoma (BCBL)-1, under the lytic cycle by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment. To elucidate the antiviral mechanism of alloferon, we tested calcium influx and the activation of the extracellular signal-regulated kinase (ERK) pathway. Furthermore, we evaluated the cytotoxicity of NK cells against BCBL-1 by alloferon.
Results:
Alloferon effectively recovered the suppressed proliferation of BCBL-1 by TPA, which was achieved by the down-regulation of lytic-cycle-related viral genes, RTA, K8 and vIRF2. To clarify the signal transduction pathways related to the regulation of the viral genes by alloferon, we confirmed that the calcium influx into BCBL-1 was apparently inhibited by alloferon, which preceded the suppression of the phosphorylation of ERK and the activation of AP-1 by TPA. Moreover, when NK cells were exposed to alloferon, their cytolytic activity was improved, and this was mediated by the enhancement of perforin/granzyme secretion.
Conclusions:
The results of this study suggest that alloferon can be used as an effective antiviral agent for the regulation of the KSHV life cycle by the down-regulation of AP-1 activity and for the the enhancement of antiviral immunity by up-regulation of NK cell cytotoxicity.
Insights
Alloferon, an immunomodulatory peptide, effectively regulates Kaposi's sarcoma-associated herpesvirus (KSHV) by inhibiting viral gene expression and enhancing natural killer (NK) cell activity. This peptide shows promise as an antiviral agent against KSHV.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Alloferon is an immunomodulatory peptide with known antiviral properties against herpesviruses.
- Kaposi's sarcoma-associated herpesvirus (KSHV) is a significant human oncogenic herpesvirus.
- Understanding alloferon's impact on KSHV is crucial for developing novel antiviral therapies.
Purpose of the Study:
- To investigate alloferon's effect on the KSHV life cycle.
- To elucidate the underlying mechanisms of alloferon's antiviral action.
- To assess alloferon's impact on natural killer (NK) cell-mediated antiviral immunity.
Main Methods:
- KSHV-infected BCBL-1 cells were treated to induce the lytic cycle.
- Cell proliferation and viral gene expression were analyzed.
- Calcium influx, ERK pathway activation, and NK cell cytotoxicity were evaluated.
Main Results:
- Alloferon suppressed KSHV lytic gene expression (RTA, K8, vIRF2) and recovered cell proliferation.
- Alloferon inhibited TPA-induced calcium influx, ERK phosphorylation, and AP-1 activation.
- Alloferon enhanced NK cell cytotoxicity via increased perforin/granzyme secretion.
Conclusions:
- Alloferon effectively regulates the KSHV life cycle by down-regulating AP-1 activity.
- Alloferon enhances antiviral immunity by up-regulating NK cell cytotoxicity.
- Alloferon demonstrates potential as an antiviral agent against KSHV.
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