16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

NON-INFECTIOUS PAPILLOMA VIRUS - LIKE PARTICLES (VLPS) INHIBIT HIV REPLICATION: IMPLICATIONS FOR IMMUNE CONTROL OF HIV REPLICATION BY IL-27

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. ThAa0102

Fakruddin J.M.¹, Lempicki R.², Yang J.², Adelsberger J.³, Pineres A.⁴, Pinto L.⁴, Lane H.C.⁵, Imamichi T.^1
1 Laboratory of Human Retrovirology, SAIC/NCI-Frederick, Frederick, United States, ² Laboratory of Immunopathogenesis and Bioinformatics, SAIC/NCI-Frederick, Frederick, United States, ³ AIDS Monitoring Laboratory, SAIC/NCI-Frederick, Frederick, United States, ⁴ HPV Monitoring Laboratory, SAIC/NCI-Frederick, Frederick, United States, ⁵ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States

BACKGROUND: Human papilloma virus (HPV)-like particles (VLPs) have been used as a vaccine to prevent HPV infection. Recent studies show that VLPs bind to dendritic cells and induce the expression of anti-viral cytokines such as IFN-α, IL-10 and IFN-γ. In this study, we evaluated the effect of VLP on HIV-1 replication in PBMCs, CD4+ T cells and macrophages from normal donors.

METHODS: Cells were infected with X4 (HIV-1NL4.3) or R5 (HIV-1AD8) virus, and then cultured for 7-days in the presence of VLP. HIV replication was monitored using a p24 antigen assay. VLP conditioned media were prepared by incubating cultures of uninfected PBMCs or macrophages in the presence or absence of VLP (1μg/ml) for 1.5 days and collecting the supernatant. Affymetrix U133+2.0 microarrays were used for gene expression analysis. Microarray validation was carried out by RT-PCR and ELISA.

RESULTS: VLP inhibited HIV-1 replication in a dose dependent manner by more than 99% and 93% in PBMC cultures infected with X4 and R5 HIV-1 strains respectively. Of interest, VLP inhibited HIV replication in macrophages by near 95% but not in CD4+ T cells. In addition, soluble factors released by PBMCs or macrophages upon VLP treatment inhibited HIV-1NL4.3 replication in T lymphocytes. Microarray analysis showed that VLP treatment increased transcripts of IL-27 and IFN-α by 14 and 140 fold respectively. VLP treatment enhanced the production of IL-27 up to 25 ng/ml, however, IFN-α levels were only 40 pg/ml. Studies on effect of IL-27 on HIV-1 replication showed that recombinant IL-27 inhibited HIV-1 in PBMCs, macrophages and CD4+ T cells up to 80% at 50 ng/ml.

CONCLUSIONS: The identification of IL-27 as a novel anti-HIV-1 cytokine along with a better understanding of the molecular mechanism of action of IL-27 may lead to the rational design of a new immune-based therapy against HIV-1 infection.

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2006-08-13
ThAa0102

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