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. 1994 Mar;95(3):442–449. doi: 10.1111/j.1365-2249.1994.tb07016.x

HIV-1 induces tumour necrosis factor and IL-1 gene expression in primary human macrophages independent of productive infection.

G Herbein 1, S Keshav 1, M Collin 1, L J Montaner 1, S Gordon 1
PMCID: PMC1535095  PMID: 7511077

Abstract

Cytokines such as tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta may play a role in immunopathogenesis of AIDS. We studied early effects (0.5-48 h) of monocytotropic (ADA) or lymphotropic (IIIB) strains of HIV-1 on TNF-alpha and IL-1 beta mRNA expression in primary human macrophages by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Three-day-old monocyte-derived macrophages were exposed either to tissue culture supernatants containing virus (at multiplicity of infection (m.o.i.) of 0.05) or to control supernatants free of virions and gp120. ADA strain, but not IIIB, replicated in primary tissue culture-differentiated macrophages (TCDM). Soluble CD4 (sCD4) was used to inhibit binding of both strains to macrophages. We found that TNF-alpha and IL-1 beta gene expression was induced by both strains 0.5-3 h after addition of virus, and that enhanced expression of both cytokines was inhibited by sCD4. We conclude that CD4-dependent binding to the cell surface is sufficient to enhance TNF-alpha and IL-1 beta mRNA, whereas productive viral replication in primary human macrophages is not required. Therefore, similar pathways regulate gene expression of TNF-alpha and IL-1 beta by macrophages during initial infection by HIV-1 in vitro.

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Selected References

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  1. Aderka D., Holtmann H., Toker L., Hahn T., Wallach D. Tumor necrosis factor induction by Sendai virus. J Immunol. 1986 Apr 15;136(8):2938–2942. [PubMed] [Google Scholar]
  2. Arend W. P., Gordon D. F., Wood W. M., Janson R. W., Joslin F. G., Jameel S. IL-1 beta production in cultured human monocytes is regulated at multiple levels. J Immunol. 1989 Jul 1;143(1):118–126. [PubMed] [Google Scholar]
  3. Bender B. S., Davidson B. L., Kline R., Brown C., Quinn T. C. Role of the mononuclear phagocyte system in the immunopathogenesis of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Rev Infect Dis. 1988 Nov-Dec;10(6):1142–1154. doi: 10.1093/clinids/10.6.1142. [DOI] [PubMed] [Google Scholar]
  4. Berman M. A., Sandborg C. I., Calabia B. S., Andrews B. S., Friou G. J. Interleukin 1 inhibitor masks high interleukin 1 production in acquired immunodeficiency syndrome (AIDS). Clin Immunol Immunopathol. 1987 Jan;42(1):133–140. doi: 10.1016/0090-1229(87)90180-2. [DOI] [PubMed] [Google Scholar]
  5. Beutler B., Cerami A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature. 1986 Apr 17;320(6063):584–588. doi: 10.1038/320584a0. [DOI] [PubMed] [Google Scholar]
  6. Burchett S. K., Weaver W. M., Westall J. A., Larsen A., Kronheim S., Wilson C. B. Regulation of tumor necrosis factor/cachectin and IL-1 secretion in human mononuclear phagocytes. J Immunol. 1988 May 15;140(10):3473–3481. [PubMed] [Google Scholar]
  7. COHN Z. A., BENSON B. THE IN VITRO DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES. II. THE INFLUENCE OF SERUM ON GRANULE FORMATION, HYDROLASE PRODUCTION, AND PINOCYTOSIS. J Exp Med. 1965 May 1;121:835–848. doi: 10.1084/jem.121.5.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Collin M., James W., Gordon S. Development of techniques to analyse the formation of HIV provirus in primary human macrophages. Res Virol. 1991 Mar-Jun;142(2-3):105–112. doi: 10.1016/0923-2516(91)90045-5. [DOI] [PubMed] [Google Scholar]
  9. Dinarello C. A. Biology of interleukin 1. FASEB J. 1988 Feb;2(2):108–115. [PubMed] [Google Scholar]
  10. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
  11. Gendelman H. E., Baca L. M., Husayni H., Turpin J. A., Skillman D., Kalter D. C., Orenstein J. M., Hoover D. L., Meltzer M. S. Macrophage-HIV interaction: viral isolation and target cell tropism. AIDS. 1990 Mar;4(3):221–228. [PubMed] [Google Scholar]
  12. Gendelman H. E., Narayan O., Kennedy-Stoskopf S., Kennedy P. G., Ghotbi Z., Clements J. E., Stanley J., Pezeshkpour G. Tropism of sheep lentiviruses for monocytes: susceptibility to infection and virus gene expression increase during maturation of monocytes to macrophages. J Virol. 1986 Apr;58(1):67–74. doi: 10.1128/jvi.58.1.67-74.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gendelman H. E., Orenstein J. M., Martin M. A., Ferrua C., Mitra R., Phipps T., Wahl L. A., Lane H. C., Fauci A. S., Burke D. S. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J Exp Med. 1988 Apr 1;167(4):1428–1441. doi: 10.1084/jem.167.4.1428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Harbison M. A., Gillis J. M., Pinkston P., Byrn R. A., Rose R. M., Hammer S. M. Effects of recombinant soluble CD4 (rCD4) on HIV-1 infection of monocyte/macrophages. J Infect Dis. 1990 Jan;161(1):1–6. doi: 10.1093/infdis/161.1.1. [DOI] [PubMed] [Google Scholar]
  15. Kalter D. C., Nakamura M., Turpin J. A., Baca L. M., Hoover D. L., Dieffenbach C., Ralph P., Gendelman H. E., Meltzer M. S. Enhanced HIV replication in macrophage colony-stimulating factor-treated monocytes. J Immunol. 1991 Jan 1;146(1):298–306. [PubMed] [Google Scholar]
  16. Klatzmann D., Barré-Sinoussi F., Nugeyre M. T., Danquet C., Vilmer E., Griscelli C., Brun-Veziret F., Rouzioux C., Gluckman J. C., Chermann J. C. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. doi: 10.1126/science.6328660. [DOI] [PubMed] [Google Scholar]
  17. Lepe-Zuniga J. L., Mansell P. W., Hersh E. M. Idiopathic production of interleukin-1 in acquired immune deficiency syndrome. J Clin Microbiol. 1987 Sep;25(9):1695–1700. doi: 10.1128/jcm.25.9.1695-1700.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lähdevirta J., Maury C. P., Teppo A. M., Repo H. Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome. Am J Med. 1988 Sep;85(3):289–291. doi: 10.1016/0002-9343(88)90576-1. [DOI] [PubMed] [Google Scholar]
  19. McKeating J. A., McKnight A., Moore J. P. Differential loss of envelope glycoprotein gp120 from virions of human immunodeficiency virus type 1 isolates: effects on infectivity and neutralization. J Virol. 1991 Feb;65(2):852–860. doi: 10.1128/jvi.65.2.852-860.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Merrill J. E., Koyanagi Y., Chen I. S. Interleukin-1 and tumor necrosis factor alpha can be induced from mononuclear phagocytes by human immunodeficiency virus type 1 binding to the CD4 receptor. J Virol. 1989 Oct;63(10):4404–4408. doi: 10.1128/jvi.63.10.4404-4408.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Merrill J. E., Koyanagi Y., Zack J., Thomas L., Martin F., Chen I. S. Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type 1. J Virol. 1992 Apr;66(4):2217–2225. doi: 10.1128/jvi.66.4.2217-2225.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Molina J. M., Scadden D. T., Byrn R., Dinarello C. A., Groopman J. E. Production of tumor necrosis factor alpha and interleukin 1 beta by monocytic cells infected with human immunodeficiency virus. J Clin Invest. 1989 Sep;84(3):733–737. doi: 10.1172/JCI114230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Molina J. M., Schindler R., Ferriani R., Sakaguchi M., Vannier E., Dinarello C. A., Groopman J. E. Production of cytokines by peripheral blood monocytes/macrophages infected with human immunodeficiency virus type 1 (HIV-1). J Infect Dis. 1990 May;161(5):888–893. doi: 10.1093/infdis/161.5.888. [DOI] [PubMed] [Google Scholar]
  24. Montaner L. J., Doyle A. G., Collin M., Herbein G., Illei P., James W., Minty A., Caput D., Ferrara P., Gordon S. Interleukin 13 inhibits human immunodeficiency virus type 1 production in primary blood-derived human macrophages in vitro. J Exp Med. 1993 Aug 1;178(2):743–747. doi: 10.1084/jem.178.2.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Munis J. R., Kornbluth R. S., Guatelli J. C., Richman D. D. Ordered appearance of human immunodeficiency virus type 1 nucleic acids following high multiplicity infection of macrophages. J Gen Virol. 1992 Aug;73(Pt 8):1899–1906. doi: 10.1099/0022-1317-73-8-1899. [DOI] [PubMed] [Google Scholar]
  26. Munis J. R., Richman D. D., Kornbluth R. S. Human immunodeficiency virus-1 infection of macrophages in vitro neither induces tumor necrosis factor (TNF)/cachectin gene expression nor alters TNF/cachectin induction by lipopolysaccharide. J Clin Invest. 1990 Feb;85(2):591–596. doi: 10.1172/JCI114478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nathan C. F. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  30. Roy S., Fitz-Gibbon L., Poulin L., Wainberg M. A. Infection of human monocytes/macrophages by HIV-1: effect on secretion of IL-1 activity. Immunology. 1988 Jun;64(2):233–239. [PMC free article] [PubMed] [Google Scholar]
  31. Stevenson H. C., Dekaban G. A., Miller P. J., Benyajati C., Pearson M. L. Analysis of human blood monocyte activation at the level of gene expression. Expression of alpha interferon genes during activation of human monocytes by poly IC/LC and muramyl dipeptide. J Exp Med. 1985 Mar 1;161(3):503–513. doi: 10.1084/jem.161.3.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vyakarnam A., McKeating J., Meager A., Beverley P. C. Tumour necrosis factors (alpha, beta) induced by HIV-1 in peripheral blood mononuclear cells potentiate virus replication. AIDS. 1990 Jan;4(1):21–27. doi: 10.1097/00002030-199001000-00003. [DOI] [PubMed] [Google Scholar]
  33. Wahl L. M., Corcoran M. L., Pyle S. W., Arthur L. O., Harel-Bellan A., Farrar W. L. Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1. Proc Natl Acad Sci U S A. 1989 Jan;86(2):621–625. doi: 10.1073/pnas.86.2.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Webb D. S., Shimizu Y., Van Seventer G. A., Shaw S., Gerrard T. L. LFA-3, CD44, and CD45: physiologic triggers of human monocyte TNF and IL-1 release. Science. 1990 Sep 14;249(4974):1295–1297. doi: 10.1126/science.1697984. [DOI] [PubMed] [Google Scholar]
  35. Wright S. C., Jewett A., Mitsuyasu R., Bonavida B. Spontaneous cytotoxicity and tumor necrosis factor production by peripheral blood monocytes from AIDS patients. J Immunol. 1988 Jul 1;141(1):99–104. [PubMed] [Google Scholar]
  36. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]

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