Volume 68, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Dengue (DEN) virus is responsible for one of the most significant viral diseases in tropical countries. Monocytes/macrophages (Mo/Mϕ) are the major target cells for DEN virus. To determine the effects of the interaction between DEN virus and Mo/Mϕ, human monocyte cultures were infected with DEN virus type 2. Apoptosis and production of tumor necrosis factor-α (TNF-α) and nitric oxide were measured in control and infected cultures. Virus was taken up by phagocytosis, but no membrane-coated pits at the virus attachment sites were observed. Increased number of apoptotic cells and increased production of TNF-α were observed in infected monocyte cultures. No increase in production of nitric oxide was observed. These results may be related to early primary viral infection, in which virus could induce apoptosis in monocytes, but monocytes may contribute to host defense mechanisms against virus by viral phagocytosis, phagocytosis of infected apoptotic cells, and the release of proinflammatory cytokines.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Gubler DJ, 1998. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 11 : 480–496. [Google Scholar]
  2. Halstead SB, O’Rourke EJ, Allinson AC, 1977. Dengue virus and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection. J Exp Med 146 : 218–229. [Google Scholar]
  3. Halstead SB, 1988. Pathogenesis of dengue: challenges to molecular biology. Science 239 : 476–481. [Google Scholar]
  4. Anderson R, Wang S, Osiowy C, Issekutz AC, 1997. Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes. J Virol 71 : 4226–4232. [Google Scholar]
  5. Chang DM, Shaio MF, 1994. Production of interleukin-1 (IL-1) and IL-1 inhibitor by human monocyte exposed to dengue virus. J Infect Dis 170 : 811–817. [Google Scholar]
  6. Shaio MF, Cheng SN, Yuh YS, Yang KD, 1995. Cytotoxic factor released by dengue virus-infected human monocytes. J Med Virol 46 : 216–223. [Google Scholar]
  7. Vaux D, Gordon S, 1985. Intracellular events during phagocytosis. Dean RT, Jessup W, eds. Mononuclear Phagocytes: Physiology and Pathology. New York: Elsevier, 5-25.
  8. Marianneau P, Steffan AM, Royer C, Drouet MT, Jaeck D, Kirn A, Deubel V, 1999. Infection of primary cultures of human Kupffer cells by dengue virus: No viral progeny synthesis, but cytokine production is evident. J Virol 73 : 5201–5206. [Google Scholar]
  9. Avirutnan P, Malasit P, Selinger B, Bhakdi S, Husmann M, 1998. Dengue virus infection of human endothelial cells leads to chemokine production, complement activation and apoptosis. J Immunol 161 : 6338–6346. [Google Scholar]
  10. Gavrieli Y, Sherman Y, Ben-Sasson SA, 1992. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119 : 493–501. [Google Scholar]
  11. Stuehr DJ, Gross SS, Sakuma I, Levi R, Nathan C, 1989. Activated murine macrophages secrete a metabolite of arginine with the bioactivity of the endothelium-derived relaxing factor and the chemical reactivity of nitric oxide. J Exp Med 169 : 1011–1023. [Google Scholar]
  12. Kittigul L, Meethien N, Sujirarat D, Kittigul C, Vasanavat S, 1997. Comparison of dengue virus antigens in the serum and peripheral blood mononuclear cells from dengue infected patients. Asian Pac J Allergy Immunol 15 : 187–191. [Google Scholar]
  13. Pauza CD, Price TM, 1988. Human immunodeficiency virus infection of T cells and monocytes proceeds via receptor-mediated endocytosis. J Cell Biol 107 : 959–968. [Google Scholar]
  14. Hotta H, Wiharta AS, Hotta S, Homma M, 1984. Dengue type 2 virus infection in human peripheral blood monocyte cultures. Microbiol Immunol 28 : 1099–1109. [Google Scholar]
  15. Brideau AD, Enquist LW, Tirabassi RS, 2000. The role of viron membrane protein endocytosis in the herpesvirus life cycle. J Clin Virol 17 : 69–82. [Google Scholar]
  16. Se-Thoe SY, Ling AE, Ng NM, 2000. Alteration of virus entry: a neutralisation mechanism for dengue-2 virus. J Med Virol 62 : 364–376. [Google Scholar]
  17. O’Sullivan MA, Killen HM, 1994. The differentiation state of monocytic cells affects their susceptibility to infection and the effects of infection by dengue virus. J Gen Virol 75 : 2387–2392. [Google Scholar]
  18. Després P, Flamand M, Ceccaldi PE, Deubel V, 1996. Human isolates of dengue type 1 virus induce apoptosis in mouse neuroblastoma cells. J Virol 70 : 4090–4096. [Google Scholar]
  19. Marianneau P, Cardona A, Edelman L, Deubel V, Després V, 1997. Dengue virus replication in human hepatoma cells activates NF-kB which in turn induces apoptotic cell death. J Virol 71 : 3244–3249. [Google Scholar]
  20. Koyama AH, Fukumori T, Fujita M, Irie H, Adachi A, 2000. Physiological significance of apoptosis in animal virus infection. Microbes Infect 2 : 1111–1117. [Google Scholar]
  21. Falasca L, Bergamini A, Serafino A, Balabaud C, Dini L, 1996. Human Kuffer cell recognition and phagocytosis of apoptotic peripheral blood lymphocytes. Exp Cell Res 224 : 152–162. [Google Scholar]
  22. Persidsky Y, Steffan AM, Gendrault JL, Hurtrel B, Berger S, Roger C, Stutte HJ, Muchmore G, Aubertin AM, Kirn A, 1995. Permissiveness of Kupffer cell for simian immunodeficiency virus (SIV) and morphologic changes in the liver of rhesus monkeys at different periods of SIV infection. Hepatology 21 : 1215–1225. [Google Scholar]
  23. Decker K, 1990. Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem 192 : 245–261. [Google Scholar]
  24. Chaturvedi UC, Elbishbishi EA, Agarwal R, Raghupathy R, Nagar R, Tandon R, Pacsa AS, Younis OI, Azizieh F, 1999. Sequential production of cytokines by dengue virus-infected human peripheral blood leukocyte cultures. J Med Virol 59 : 335–340. [Google Scholar]
  25. Khare M, Chaturvedi UC, 1997. Role of nitric oxide in transmission of dengue virus specific suppressor signal. Indian J Exp Biol 35 : 855–860. [Google Scholar]
  26. Kurane I, Ennis FA, 1994. Cytokines in dengue virus infection: role of cytokines in the pathogenesis of dengue hemorrhagic fever. Semin Virol 5 : 443–448. [Google Scholar]
  27. Niwa M, Hara A, Kanamori Y, Hatakeyama D, Saito M, Takami T, Matsuno H, Kozawa O, Uematsu T, 2000. Nuclear Factor-kappa B activates dual inhibition sites in the regulation of tumor necrosis factor-alpha-induced neutrophil apoptosis. Eur J Pharmacol 407 : 211–219. [Google Scholar]
  28. Jaeschke H, Farhood A, Cai SX, Tseng BY, Bajt AL, 2000. Protection against TNF-induced liver parenchymal cell apoptosis during endotoxemia by a novel caspase inhibitor in mice. Toxicol Appl Pharmacol 169 : 77–83. [Google Scholar]
  29. van Strijp JA, van der Tol ME, Miltenburg LA, van Kessel KP, Verhoef J, 1991. Tumor necrosis factor triggers granulocytes to internalize complement-coated virus particles. Immunology 73 : 77–82. [Google Scholar]
  30. Kittigul L, Temprom W, Sujirarat D, Kittigul C, 2000. Determination of tumor necrosis factor-alpha levels in dengue virus infected patients by a sensitive biotin-streptavidin enzyme-linked immunosorbent assay. J Virol Methods 90 : 51–57. [Google Scholar]
  31. Hober D, Nguyen TL, Shen L, Ha DQ, Huong VT, Benyoucef S, Nguyen TH, Bui TM, Loan HK, Le BL, Bouzidi A, De Groote D, Drouet MT, Deubel V, Wattre P, 1998. Tumor necrosis factor alpha levels in plasma and whole blood culture in dengue-infected patients: relationship between virus detection and pre-existing specific antibodies. J Med Virol 54 : 210–218. [Google Scholar]
  32. Lee DH, Tam SS, Benyoucef S, de Groote D, Deubel V, Wattre P, 1996. Enhanced TNF alpha production by monocytic-like cells exposed to dengue virus antigen. Immunol Lett 53 : 115–120. [Google Scholar]
  33. Bhakdi S, Kazatchkine MD, 1990. Pathogenesis of dengue: an alternative hypothesis. Southeast Asian J Trop Med Public Health 21 : 652–657. [Google Scholar]
  34. Daughaday CC, Brandt WE, McCown JM, Russel PK, 1981. Evidence for two mechanisms of dengue virus infection of adherent human monocytes: trypsin-sensitive virus receptors and trypsin-resistant immune complex receptors. Infect Immun 32 : 469–473. [Google Scholar]

Data & Media loading...

  • Received : 25 Apr 2001
  • Accepted : 21 Mar 2002

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error