Expression of the interleukin-18 gene from rhesus macaque by the simian immunodeficiency virus does not result in increased viral replication

L. D. Giavedoni, J. D. Imhoof, M. C. Velasquillo, L. M. Parodi, V. L. Hodara

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    Abstract

    Interleukin-18 (IL-18), previously known as interferon-γ (IFN-γ)-inducing factor (IGIF), is a proinflammatory cytokine expressed by activated macrophages that acts in synergy with IL-12 as an important amplifying factor for IFN-γ production and Th1 development. To study the effect of IL-18 on a lentiviral infection, we cloned the IL-18 gene from a rhesus macaque and constructed replication-competent simian immunodeficiency virus (SIV) that expressed either the precursor pro-IL-18 (SIVIL-18) or the mature form (SIVmIL-18) of IL-18. The predicted amino acid sequence for rhesus IL-18 had 96% homology with the human one, differing in only 8 of 193 residues. SIVIL-18 and SIVmIL-18 replicated more slowly than control viruses in the CEM × 3174 cell line and resulted in the development of chronically infected cell lines that expressed high levels of infectious SIV. The cell line generated by SIVIL-18 released large quantities of IL-18 into the supernatant, whereas the one obtained from SIVmIL-18 showed the accumulation of IL-18 in the cytoplasm. Similarly, SIVIL-18 and SIVmIL-18 replicated more slowly than the unmodified viral vector in rhesus peripheral blood mononuclear cells (PMBC), but only SIVIL-18 expressed biologically active IL-18. These experiments show that the precursor form of IL-18 is necessary for the efficient release of the cytokine and that IL-18 does not promote increased replication of SIV in rhesus PBMC.

    Original languageEnglish (US)
    Pages (from-to)173-180
    Number of pages8
    JournalJournal of Interferon and Cytokine Research
    Volume21
    Issue number3
    DOIs
    StatePublished - Aug 6 2001

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    ASJC Scopus subject areas

    • Immunology
    • Cell Biology
    • Virology

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