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Noninfectious papilloma virus–like particles inhibit HIV-1 replication: implications for immune control of HIV-1 infection by IL-27

2006; Elsevier BV; Volume: 109; Issue: 5 Linguagem: Inglês

10.1182/blood-2006-02-001578

1528-0020

J. Mohamad Fakruddin, Richard A. Lempicki, Robert J. Gorelick, Jun Yang, Joseph W. Adelsberger, Alfonso García‐Piñeres, Lígia A. Pinto, H. Clifford Lane, Tomozumi Imamichi,

Herpesvirus Infections and Treatments

Abstract Human papilloma virus (HPV)–like particles (VLPs) have been used as a vaccine to prevent HPV infection. Recent studies demonstrate that VLPs bind to dendritic cells and induce the expression of antiviral cytokines such as interferon-α (IFN-α), interleukin-10 (IL-10) and IFN-γ. In the present study, we evaluated the effect of VLPs on HIV-1 replication in peripheral blood mononuclear cells (PBMCs), CD4+ T cells, and macrophages. Here, we show that VLPs suppress the replication of both X4 and R5 HIV-1 without affecting the expression of CD4, CXCR4, and CCR5. Soluble factor(s) released by PBMCs and macrophages on VLPs treatment inhibited HIV-1 replication. To determine the inhibitory factors, DNA microarray analysis was performed using VLP-treated PBMCs and macrophages. VLPs induced the genes associated with IFN induction, immune responses, and antiviral responses, among with the recently described cytokine IL-27. Subsequently, IL-27 was found to be a potent inhibitor of HIV-1 replication in PBMCs, CD4+ T cells, and macrophages. Taken together, our studies identify a novel role of IL-27 in restricting HIV-1 replication and suggest that further examination of the inhibitory property of IL-27 may pave the way for a novel therapy for HIV-1 infection.