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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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Submitted February 3, 2006
Accepted October 13, 2006
Non-infectious papilloma virus-like particles inhibit HIV-1 replication: implications for immune control of HIV-1 infection by IL-27
J.Mohamad Fakruddin, Richard A Lempicki, Robert J. Gorelick, Jun Yang, Joseph W Adelsberger, Alfonso J Garcia-Pineres, Ligia A Pinto, H.Clifford Lane, and Tomozumi Imamichi*
Science Applications International Corporation-Frederick, Inc./National Cancer Institute-Frederick
National Institute of Allergy and Infectious Diseases, National Institutes of Health
* Corresponding author; email: timamichi{at}niaid.nih.gov.
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 (IFN)- , interleukin (IL)-10 and IFN- . 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 upon VLPs treatment inhibited HIV-1 replication. To determine the inhibitory factors, DNA microarray analysis was performed using VLPs-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 PBMC, 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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