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Abstract

For some time there has been evidence suggesting an interaction between human cytomegalovirus (HCMV) and (HIV) in the pathogenesis of AIDS. Here, the interaction of HCMV and HIV-1 was examined in monocyte/macrophage cells, two cell types known to be targets for both viruses . Infection experiments demonstrated that prior infection with HCMV impeded subsequent superinfection with HIV-1. In contrast, uninfected bystander cells within the population were still permissive for HIV-1 infection and were also found to express increased levels of Gag after HIV-1 superinfection. Analysis of CCR5, a co-receptor for HIV-1, on HCMV-infected and bystander cells showed a substantial loss of surface CCR5 expression on infected cells due to HCMV-induced reduction of total cellular CCR5. In contrast, uninfected bystander cells displayed increased surface CCR5 expression. Furthermore, the data suggested that soluble factor(s) secreted from HCMV-infected cells were responsible for the observed upregulation of CCR5 on uninfected bystander cells. Taken together, these results suggest that, whilst HCMV-infected monocytes/macrophages are refractory to infection with HIV-1, HCMV-uninfected bystander cells within a population are more susceptible to HIV-1 infection. On this basis, HCMV infection may contribute to the pathogenesis of HIV-1.

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/content/journal/jgv/10.1099/vir.0.81452-0
2006-08-01
2025-05-12
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References

  1. Algeciras-Schimnich A., Vlahakis S. R., Villasis-Keever A., Gomez T., Heppelmann C. J., Bou G., Paya C. V. 2002; CCR5 mediates Fas- and caspase-8 dependent apoptosis of both uninfected and HIV infected primary human CD4 T cells. AIDS 16:1467–1478 [CrossRef]
    [Google Scholar]
  2. Asin S., Bren G. D., Carmona E. M., Solan N. J., Paya C. V. 2001; NF- κ B cis -acting motifs of the human immunodeficiency virus (HIV) long terminal repeat regulate HIV transcription in human macrophages. J Virol 75:11408–11416 [CrossRef]
    [Google Scholar]
  3. Baillie J., Sahlender D. A., Sinclair J. H. 2003; Human cytomegalovirus infection inhibits tumor necrosis factor alpha (TNF- α ) signaling by targeting the 55-kilodalton TNF- α receptor. J Virol 77:7007–7016 [CrossRef]
    [Google Scholar]
  4. Croitoru-Lamoury J., Guillemin G. J., Boussin F. D. & 7 other authors 2003; Expression of chemokines and their receptors in human and simian astrocytes: evidence for a central role of TNF α and IFN γ in CXCR4 and CCR5 modulation. Glia 41:354–370 [CrossRef]
    [Google Scholar]
  5. Curran J. W., Morgan W. M., Hardy A. M., Jaffe H. W., Darrow W. W., Dowdle W. R. 1985; The epidemiology of AIDS: current status and future prospects. Science 229:1352–1357 [CrossRef]
    [Google Scholar]
  6. Davis M. G., Kenney S. C., Kamine J., Pagano J. S., Huang E.-S. 1987; Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus. Proc Natl Acad Sci U S A 84:8642–8646 [CrossRef]
    [Google Scholar]
  7. Donaghy H., Gazzard B., Gotch F., Patterson S. 2003; Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1. Blood 101:4505–4511 [CrossRef]
    [Google Scholar]
  8. Duclos H., Elfassi E., Michelson S., Arenzana-Seisdedos F., Hazan U., Munier A., Virelizier J. L. 1989; Cytomegalovirus infection and trans-activation of HIV-1 and HIV-2 LTRs in human astrocytoma cells. AIDS Res Hum Retroviruses 5:217–224 [CrossRef]
    [Google Scholar]
  9. Fairley J. A., Baillie J., Bain M., Sinclair J. H. 2002; Human cytomegalovirus infection inhibits epidermal growth factor (EGF) signalling by targeting EGF receptors. J Gen Virol 83:2803–2810
    [Google Scholar]
  10. Hariharan D., Douglas S. D., Lee B., Lai J.-P., Campbell D. E., Ho W.-Z. 1999; Interferon- γ upregulates CCR5 expression in cord and adult blood mononuclear phagocytes. Blood 93:1137–1144
    [Google Scholar]
  11. Ho W.-Z., Harouse J. M., Rando R. F., Gonczol E., Srinivasan A., Plotkin S. A. 1990; Reciprocal enhancement of gene expression and viral replication between human cytomegalovirus and human immunodeficiency virus type 1. J Gen Virol 71:97–103 [CrossRef]
    [Google Scholar]
  12. Jault F. M., Spector S. A., Spector D. H. 1994; The effects of cytomegalovirus on human immunodeficiency virus replication in brain-derived cells correlate with permissiveness of the cells for each virus. J Virol 68:959–973
    [Google Scholar]
  13. Kotenko S. V., Saccani S., Izotova L. S., Mirochnitchenko O. V., Pestka S. 2000; Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10. Proc Natl Acad Sci U S A 97:1695–1700 [CrossRef]
    [Google Scholar]
  14. Koval V., Clark C., Vaishnav M., Spector S. A., Spector D. H. 1991; Human cytomegalovirus inhibits human immunodeficiency virus replication in cells productively infected by both viruses. J Virol 65:6969–6978
    [Google Scholar]
  15. Koval V., Jault F. M., Pal P. G., Moreno T. N., Aiken C., Trono D., Spector S. A., Spector D. H. 1995; Differential effects of human cytomegalovirus on integrated and unintegrated human immunodeficiency virus sequences. J Virol 69:1645–1651
    [Google Scholar]
  16. Lathey J. L., Spector S. A. 1991; Unrestricted replication of human cytomegalovirus in hydrocortisone-treated macrophages. J Virol 65:6371–6375
    [Google Scholar]
  17. Lathey J. L., Spector D. H., Spector S. A. 1994; Human cytomegalovirus-mediated enhancement of human immunodeficiency virus type-1 production in monocyte-derived macrophages. Virology 199:98–104 [CrossRef]
    [Google Scholar]
  18. Lecointe D., Dugas N., Leclerc P., Hery C., Delfraissy J.-F., Tardieu M. 2002; Human cytomegalovirus infection reduces surface CCR5 expression in human microglial cells, astrocytes and monocyte-derived macrophages. Microbes Infect 4:1401–1408 [CrossRef]
    [Google Scholar]
  19. Lei J.-Q., Wu C.-L., Wang X.-L., Wang H.-H. 2005; p38 MAPK-dependent and YY1-mediated chemokine receptors CCR5 and CXCR4 up-regulation in U937 cell line infected by Mycobacterium tuberculosis or Actinobacillus actinomycetemcomitans . Biochem Biophys Res Commun 329:610–615 [CrossRef]
    [Google Scholar]
  20. Meltzer M. S., Nakamura M., Hansen B. D., Turpin J. A., Kalter D. C., Gendelman H. E. 1990; Macrophages as susceptible targets for HIV infection, persistent viral reservoirs in tissue, and key immunoregulatory cells that control levels of virus replication and extent of disease. AIDS Res Hum Retroviruses 6:967–971
    [Google Scholar]
  21. Moreno T. N., Fortunato E. A., Hsia K., Spector S. A., Spector D. H. 1997; A model system for human cytomegalovirus-mediated modulation of human immunodeficiency virus type 1 long terminal repeat activity in brain cells. J Virol 71:3693–3701
    [Google Scholar]
  22. Moriuchi M., Moriuchi H. 2001; Octamer transcription factors up-regulate the expression of CCR5, a coreceptor for HIV-1 entry. J Biol Chem 276:8639–8642 [CrossRef]
    [Google Scholar]
  23. Moriuchi M., Moriuchi H. 2003; YY1 transcription factor down-regulates expression of CCR5, a major coreceptor for HIV-1. J Biol Chem 278:13003–13007 [CrossRef]
    [Google Scholar]
  24. Moriuchi H., Moriuchi M., Fauci A. S. 1997; Cloning and analysis of the promoter region of CCR5, a coreceptor for HIV-1 entry. J Immunol 159:5441–5449
    [Google Scholar]
  25. Murphy J. C., Fischle W., Verdin E., Sinclair J. H. 2002; Control of cytomegalovirus lytic gene expression by histone acetylation. EMBO J 21:1112–1120 [CrossRef]
    [Google Scholar]
  26. Nelson J. A., Reynolds-Kohler C., Oldstone M. B., Wiley C. A. 1988; HIV and HCMV coinfect brain cells in patients with AIDS. Virology 165:286–290 [CrossRef]
    [Google Scholar]
  27. Percherancier Y., Planchenault T., Valenzuela-Fernandez A., Virelizier J.-L., Arenzana-Seisdedos F., Bachelerie F. 2001; Palmitoylation-dependent control of degradation, life span, and membrane expression of the CCR5 receptor. J Biol Chem 276:31936–31944 [CrossRef]
    [Google Scholar]
  28. Peterson P. K., Gekker G., Chao C. C., Hu S., Edelman C., Balfour H. H. Jr, Verhoef J. 1992; Human cytomegalovirus-stimulated peripheral blood mononuclear cells induce HIV-1 replication via a tumor necrosis factor- α -mediated mechanism. J Clin Invest 89:574–580 [CrossRef]
    [Google Scholar]
  29. Pleskoff O., Tréboute C., Brelot A., Heveker N., Seman M., Alizon M. 1997; Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry. Science 276:1874–1878 [CrossRef]
    [Google Scholar]
  30. Rando R. F., Srinivasan A., Feingold J., Gonczol E., Plotkin S. 1990; Characterization of multiple molecular interactions between human cytomegalovirus (HCMV) and human immunodeficiency virus type. 1 (HIV-1). Virology 17687–97 [CrossRef]
  31. Reeves M. B., MacAry P. A., Lehner P. J., Sissons J. G. P., Sinclair J. H. 2005; Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers. Proc Natl Acad Sci U S A 102:4140–4145 [CrossRef]
    [Google Scholar]
  32. Sinclair J., Baillie J., Bryant L., Caswell R. 2000; Human cytomegalovirus mediates cell cycle progression through G1 into early S phase in terminally differentiated cells. J Gen Virol 81:1553–1565
    [Google Scholar]
  33. Sinzger C., Kahl M., Laib K., Klingel K., Rieger P., Plachter B., Jahn G. 2000; Tropism of human cytomegalovirus for endothelial cells is determined by a post-entry step dependent on efficient translocation to the nucleus. J Gen Virol 81:3021–3035
    [Google Scholar]
  34. Spencer J. V., Lockridge K. M., Barry P. A., Lin G., Tsang M., Penfold M. E. T., Schall T. J. 2002; Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10. J Virol 76:1285–1292 [CrossRef]
    [Google Scholar]
  35. Suzuki S., Miyagi T., Chuang L. F., Yau P. M., Doi R. H., Chuang R. Y. 2002; Chemokine receptor CCR5: polymorphism at protein level. Biochem Biophys Res Commun 296:477–483 [CrossRef]
    [Google Scholar]
  36. Turtinen L. W., Seufzer B. J. 1994; Selective permissiveness of TPA differentiated THP-1 myelomonocytic cells for human cytomegalovirus strains AD169 and Towne. Microb Pathog 16:373–378 [CrossRef]
    [Google Scholar]
  37. Tyner J. W., Uchida O., Kajiwara N. & 8 other authors 2005; CCL5–CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Nat Med 11:1180–1187 [CrossRef]
    [Google Scholar]
  38. Varani S., Frascaroli G., Homman-Loudiyi M., Feld S., Landini M. P., Söderberg-Nauclér C. 2005; Human cytomegalovirus inhibits the migration of immature dendritic cells by down-regulating cell-surface CCR1 and CCR5. J Leukoc Biol 77:219–228
    [Google Scholar]
  39. Walker S., Hagemeier C., Sissons J. G. P., Sinclair J. H. 1992; A 10-base-pair element of the human immunodeficiency virus type 1 long terminal repeat (LTR) is an absolute requirement for transactivation by the human cytomegalovirus 72-kilodalton IE1 protein but can be compensated for by other LTR regions in transactivation by the 80-kilodalton IE2 protein. J Virol 66:1543–1550
    [Google Scholar]
  40. Webster A. 1991; Cytomegalovirus as a possible cofactor in HIV disease progression. J Acquir Immune Defic Syndr 4 (Suppl. 1):S47–S52
    [Google Scholar]
  41. Weinshenker B. G., Wilton S., Rice G. P. 1988; Phorbol ester-induced differentiation permits productive human cytomegalovirus infection in a monocytic cell line. J Immunol 140:1625–1631
    [Google Scholar]
  42. Weissman D., Dybul M., Daucher M. B., Davey R. T. Jr, Walker R. E., Kovacs J. A. 2000; Interleukin-2 up-regulates expression of the human immunodeficiency virus fusion coreceptor CCR5 by CD4+ lymphocytes in vivo. J Infect Dis 181:933–938 [CrossRef]
    [Google Scholar]
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