Abstract
Interleukin-16 (IL-16) is secreted by activated CD8+ T lymphocytes and acts on CD4+ T lymphocytes, monocytes and eosinophils. Recently, the C-terminal 130-amino acid portion of IL-16 was shown to suppress HIV-1 replication in vitro. To explore the potential of human IL-16 for gene therapy, this portion was transfected into HIV-1-susceptible CD4+ Jurkat cells by means of a mammalian expression vector. The stable transfectants synthesized and secreted IL-16 protein. The expression of IL-16 did not alter growth rate and CD4 expression; however, HIV replication was inhibited by as much as 99%. Furthermore, during the initial phase of the infection, equal amounts of HIV-1 proviral DNA were found in cells transfected with IL-16 and with vector alone. In contrast, the 2-kilobase HIV-1 transcripts were markedly reduced and the 4-kb and 9-kb transcripts were undetectable in the cells transfected with IL-16.These findings indicate that IL-16-mediated inhibition of HIV-1 is not at the level of viral entry or reverse transcription, but at messenger RNA expression.
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References
Center, D.M. & Cruikshank, W. Modulation of lymphocyte migration by human lymphokines. I. Identification and characterization of chemoattractant activity for lymphocytes. J. Immunol. 128, 2563–2568 (1982).
Cruikshank, W. & Center, D.M. Modulation of lymphocyte migration by human lymphokines. II. Purification of a lymphotactic factor (LCF). J. Immunol. 128, 2569–2574 (1982).
Cruikshank, W.W., Berman, J.S., Theodore, A.C., Bernardo, J. & Center, D.M. Lymphocyte activation of T4+ T lymphocytes and monocytes. J. Immunol. 138, 3817–3825 (1987).
Rand, T., Cruikshank, W.W., Center, D.M. & Weller, P.F. CD4-mediated stimulation of human eosinophils: Lymphocyte chemoattractant factor and other CD4-binding ligands elicit eosinophil migration. J. Exp. Med. 173, 1521–1528 (1991).
Cruikshank, W.W., Greenstein, J.L., Theodore, A.C. & Center, D.M. Lymphocyte chemoattractant factor induces CD4-dependent intracytoplasmic signaling in lymphocytes. J. Immunol. 146, 2928–2934 (1991).
Cruikshank, W.W. et al. Molecular and functional analysis of a lymphocyte chemoattractant factor: Association of biologic function with CD4 expression. Proc. Natl. Acad. Sci. USA 91, 5109–5119 (1994).
Bazan, J.F. & Schall, T.J. Interleukin-16 or not? Nature 381, 29–30 (1996).
Bannert, N., Baier, M., Werner, A. & Kurth, R. Reply to: Interleukin-16 or not. Nature 381, 30 (1996).
Baier, M., Wermer, A., Bannert, N., Metzner, K. & Kurth, R. HIV suppression by interleukin-16. Nature 378, 563 (1995).
Walker, C.M., Moody, D.J., Stites, D.P. & Levy, J.A. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science 234, 1563–1566 (1986).
Levy, J.A. HIV pathogenesis and long-term survival. AIDS 7, 1401–1410 (1993).
Ennen, J., et al. CD8+ T lymphocytes of African Green monkeys secrete an immunodeficiency virus-suppressing lymphokine. Proc. Natl. Acad. Sci. USA 91, 7207–7211 (1994).
Laberge, S., Cruikshank, W.W., Kornfeld, H. & Center, D.M. Histamine-induced secretion of lymphocyte chemoattractant factor from CD8+ T cells is independent of transcription and translation: Evidence for constitutive protein synthesis and storage. J. Immunol. 155, 2902–2910 (1995).
Dalgleish, A.G. et al. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312, 763–767 (1984).
Larder, B.A., Darby, G. & Richman, D.D. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 243, 1731–1734 (1989).
Ponting, C.P. & Phillips, C. DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins [Letter]. Trends Biochem. Sci. 20, 102–103 (1995).
Sato, T., Irie, S., Kitada, S. & Reed, J.C. FAP-1: A protein tyrosine phosphatase that associates with Fas. Science 268, 411–415 (1995).
Oravecz, T., Pall, M. & Norcross, M.A. β-Chemokine inhibition of monocytotropic HIV-1 infection: Interference with a postbinding fusion step. J. Immunol. 157, 1329–1332 (1996).
Bleul, C.C. et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382 829–833 1996).
Obeelin, E. et al. The CXC chemokines SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 382, 833–835 (1996).
Deng, H.K. et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 381, 661–666 (1996).
Dragic, T. et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381, 667–673 (1996).
Choe, H., et al. The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85, 1135–1148 (1996).
Feng, Y., Broder, C., Kennedy, P. & Berger, E. HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272, 872–877 (1996).
Cullen, B.R. & Greene, W.C. Regulatory pathways governing HIV-1 replication. Cell 58, 423–426 (1989).
Zhou, P., Cao, H., Smart, M. & David, C. Molecular basis of genetic polymorphism in major histocompatibility complex-linked proteasome gene (Lmp-2). Proc. Natl. Acad. Sci. USA 90, 2681–2684 (1993).
Redondo, J.M., Hata, S., Brocklehurst, C. & Krangel, M.S. A T cell-specific transcriptional enhancer within the human T cell receptor δ locus. Science 247, 1225–1229 (1990).
Frees, E.O. & Martin, M.A. Evidence for a functional interaction between the V1/V2 and C4 domains of human immunodeficiency virus type 1 envelope glycoprotein gp 120. J. Virol. 68, 2503–2512 (1994).
Shaheen, F., Duan, L., Zhu, M., Bagasra, O. & Pomerantz, R.J. Targeting human immunodeficiency virus type 1 reverse transcriptase by intracellular expression of single-chain variable fragments to inhibit early stages of the viral life cycle. J. Virol. 70, 3392–3400 (1996).
Kwok, S.F. et al. Low incidence of HTLV infections in random blood donors with indeterminate Western blot patterns. Transfusion 30, 491–494 (1990).
Maniatis, T., Fritsch, E.F. & Sambrook, J. Molecular Cloning: A Laboratory Manual. (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1982).
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Zhou, P., Goldstein, S., Devadas, K. et al. Human CD4+ cells transfected with IL-16 cDNA are resistant to HIV-1 infection: Inhibition of mRNA expression. Nat Med 3, 659–664 (1997). https://doi.org/10.1038/nm0697-659
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DOI: https://doi.org/10.1038/nm0697-659
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