1887

Abstract

Chemokines regulate migration of leukocytes to sites of infection. In this work, we have shown that the chemokine RANTES/CCL5 is produced after herpes simplex virus (HSV) infection of macrophages and fibroblasts and provide data on the underlying molecular mechanism. Reporter gene assays showed HSV-induced RANTES production to be regulated at the transcriptional level. Expression of RANTES was blocked by -tosyl--phenylalanine, an inhibitor of the nuclear factor B (NF-B) pathway and also in cell lines stably expressing a dominant-negative mutant of IB kinase . Cell lines stably expressing a dominant-negative mutant of interferon regulatory factor 3 (IRF-3) also produced dramatically decreased levels of RANTES after infection compared with the control cell line. In contrast, overexpression of dominant-negative p38 and also treatment with SB203580, an inhibitor of p38, did not significantly affect expression of RANTES. Taken together, these data suggest that HSV induces transcriptional activation of the RANTES gene through the transcription factors NF-B and IRF-3.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19159-0
2003-09-01
2019-09-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/9/vir842491.html?itemId=/content/journal/jgv/10.1099/vir.0.19159-0&mimeType=html&fmt=ahah

References

  1. Casola, A., Garofalo, R. P., Haeberle, H., Elliott, T. F., Lin, R., Jamaluddin, M. & Brasier, A. R. ( 2001; ). Multiple cis regulatory elements control RANTES promoter activity in alveolar epithelial cells infected with respiratory syncytial virus. J Virol 75, 6428–6439.[CrossRef]
    [Google Scholar]
  2. Eo, S. K., Lee, S., Chun, S. & Rouse, B. T. ( 2001; ). Modulation of immunity against herpes simplex virus infection via mucosal genetic transfer of plasmid DNA encoding chemokines. J Virol 75, 569–578.[CrossRef]
    [Google Scholar]
  3. Genin, P., Algarte, M., Roof, P., Lin, R. & Hiscott, J. ( 2000; ). Regulation of RANTES chemokine gene expression requires cooperativity between NF-κB and IFN-regulatory factor transcription factors. J Immunol 164, 5352–5361.[CrossRef]
    [Google Scholar]
  4. Kujime, K., Hashimoto, S., Gon, Y., Shimizu, K. & Horie, T. ( 2000; ). p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase regulate RANTES production by influenza virus-infected human bronchial epithelial cells. J Immunol 164, 3222–3228.[CrossRef]
    [Google Scholar]
  5. Lin, R., Heylbroeck, C., Genin, P., Pitha, P. M. & Hiscott, J. ( 1999; ). Essential role of interferon regulatory factor 3 in direct activation of RANTES chemokine transcription. Mol Cell Biol 19, 959–966.
    [Google Scholar]
  6. Luster, A. D. ( 1998; ). Chemokines – chemotactic cytokines that mediate inflammation. N Engl J Med 338, 436–445.[CrossRef]
    [Google Scholar]
  7. Malmgaard, L., Paludan, S. R., Mogensen, S. C. & Ellermann-Eriksen, S. ( 2000; ). Herpes simplex virus type 2 induces secretion of IL-12 by macrophages through a mechanism involving NF-κB. J Gen Virol 81, 3011–3020.
    [Google Scholar]
  8. Melchjorsen, J., Pedersen, F. S., Mogensen, S. C. & Paludan, S. R. ( 2002; ). Herpes simplex virus selectively induces expression of the CC chemokine RANTES/CCL5 in macrophages through a mechanism dependent on PKR and ICP0. J Virol 76, 2780–2788.[CrossRef]
    [Google Scholar]
  9. Paludan, S. R. ( 2001; ). Requirements for the induction of interleukin-6 by herpes simplex virus-infected leukocytes. J Virol 75, 8008–8015.[CrossRef]
    [Google Scholar]
  10. Paludan, S. R., Ellermann-Eriksen, S. & Mogensen, S. C. ( 1998; ). NF-κB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-γ-induced nitric oxide production in macrophages. J Gen Virol 79, 2785–2793.
    [Google Scholar]
  11. Paludan, S. R., Ellermann-Eriksen, S., Kruys, V. & Mogensen, S. C. ( 2001; ). Expression of TNF-α by herpes simplex virus-infected macrophages is regulated by a dual mechanism: transcriptional regulation by NF-κB and activating transcription factor 2/Jun and translational regulation through the AU-rich region of the 3′ untranslated region. J Immunol 167, 2202–2208.[CrossRef]
    [Google Scholar]
  12. Pazdrak, K., Olszewska-Pazdrak, B., Liu, T., Takizawa, R., Brasier, A. R., Garofalo, R. P. & Casola, A. ( 2002; ). MAPK activation is involved in posttranscriptional regulation of RSV-induced RANTES gene expression. Am J Physiol Lung Cell Mol Physiol 283, L364–L372.[CrossRef]
    [Google Scholar]
  13. Preston, C. M., Harman, A. N. & Nicholl, M. J. ( 2001; ). Activation of interferon response factor-3 in human cells infected with herpes simplex virus type 1 or human cytomegalovirus. J Virol 75, 8909–8916.[CrossRef]
    [Google Scholar]
  14. Sin, J. I., Kim, J. J., Pachuk, C., Satishchandran, C. & Weiner, D. B. ( 2000; ). DNA vaccines encoding interleukin-8 and RANTES enhance antigen-specific Th1-type CD4+T-cell-mediated protective immunity against herpes simplex virus type 2 in vivo. J Virol 74, 11173–11180.[CrossRef]
    [Google Scholar]
  15. Skoldenberg, B. ( 1996; ). Herpes simplex encephalitis. Scand J Infect Dis Suppl. 100, 8–13.
    [Google Scholar]
  16. tenOever, B. R., Servant, M. J., Grandvaux, N., Lin, R. & Hiscott, J. ( 2002; ). Recognition of the measles virus nucleocapsid as a mechanism of IRF-3 activation. J Virol 76, 3659–3669.[CrossRef]
    [Google Scholar]
  17. Tumpey, T. M., Cheng, H., Cook, D. N., Smithies, O., Oakes, J. E. & Lausch, R. N. ( 1998; ). Absence of macrophage inflammatory protein-1α prevents the development of blinding herpes stromal keratitis. J Virol 72, 3705–3710.
    [Google Scholar]
  18. Whitley, R. J. & Roizman, B. ( 2001; ). Herpes simplex virus infections. Lancet 357, 1513–1518.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19159-0
Loading
/content/journal/jgv/10.1099/vir.0.19159-0
Loading

Data & Media loading...

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