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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1841-1849.
Prepublished online as a Blood First Edition Paper on October 26, 2006; DOI 10.1182/blood-2006-02-001578.


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CHEMOKINES, CYTOKINES, AND INTERLEUKINS

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

J. Mohamad Fakruddin1, Richard A. Lempicki2, Robert J. Gorelick3, Jun Yang2, Joseph W. Adelsberger4, Alfonso J. Garcia-Pineres5, Ligia A. Pinto5, H. Clifford Lane6, and Tomozumi Imamichi1

1 Laboratory of Human Retrovirology, Clinical Services Program (CSP), Science Applications International Corporation (SAIC)–Frederick, National Cancer Institute (NCI)–Frederick, MD; 2 Laboratory of Immunopathogenesis and Bioinformatics, CSP, SAIC-Frederick, NCI-Frederick, MD; 3 Retroviral Mutagenesis Section, AIDS Vaccine Program, SAIC-Frederick, NCI-Frederick, MD; 4 AIDS Monitoring Laboratory, CSP, SAIC-Frederick, NCI-Frederick, MD; 5 HPV Monitoring Laboratory, CSP, SAIC-Frederick, NCI-Frederick, MD; and 6 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

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-{alpha} (IFN-{alpha}), interleukin-10 (IL-10) and IFN-{gamma}. 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.


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J. Leukoc. Biol.Home page
J. Pirhonen, J. Siren, I. Julkunen, and S. Matikainen
IFN-{alpha} regulates Toll-like receptor-mediated IL-27 gene expression in human macrophages
J. Leukoc. Biol., November 1, 2007; 82(5): 1185 - 1192.
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