1887

Abstract

Macrophages and dendritic cells (DCs) play essential roles in host defence against microbial infections. In the present study, it is shown that human monocyte-derived macrophages and DCs express both type I and type III interferons (IFNs) [IFN-, IFN- and interleukin 28 (IL-28), IL-29, respectively], tumour necrosis factor alpha and the chemokines CCL5 and CXCL10 after herpes simplex virus 1 (HSV-1) infection. The cytokine-inducing activity of HSV-1 was dependent on viability of the virus, because UV-inactivated virus did not induce a cytokine response. Pretreatment of the cells with IFN- or IL-29 strongly enhanced the HSV-1-induced cytokine response. Both IFN- and IL-29 decreased viral immediate-early (IE) gene infected-cell protein 27 (ICP27) transcription, suggesting that IL-29 possesses antiviral activity against HSV-1 comparable to that of IFN-. Macrophage infection with HSV-1 lacking functional ICP27 (d27-1 virus) resulted in strongly enhanced cytokine mRNA expression and protein production. In contrast, viruses lacking functional IE genes ICP0 and ICP4 induced cytokine responses comparable to those of the wild-type viruses. The activation of transcription factors IRF-3 and NF-B was strongly augmented when macrophages were infected with the ICP27 mutant virus. Altogether, the results demonstrate that HSV-1 both induces and inhibits the antiviral response in human cells and that the type III IFN IL-29, together with IFN-, amplifies the antiviral response against the virus. It is further identified that viral IE-gene expression interferes with the antiviral response in human macrophages and ICP27 is identified as an important viral protein counteracting the early innate immune response.

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2006-05-01
2019-10-15
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References

  1. Ankel, H., Westra, D. F., Welling-Wester, S. & Lebon, P. ( 1998; ). Induction of interferon-α by glycoprotein D of herpes simplex virus: a possible role of chemokine receptors. Virology 251, 317–326.[CrossRef]
    [Google Scholar]
  2. Bartlett, N. W., Buttigieg, K., Kotenko, S. V. & Smith, G. L. ( 2005; ). Murine interferon lambdas (type III interferons) exhibit potent antiviral activity in vivo in a poxvirus infection model. J Gen Virol 86, 1589–1596.[CrossRef]
    [Google Scholar]
  3. Biron, C. A., Nguyen, K. B., Pien, G. C., Cousens, L. P. & Salazar-Mather, T. P. ( 1999; ). Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17, 189–220.[CrossRef]
    [Google Scholar]
  4. Coccia, E. M., Severa, M., Giacomini, E., Monneron, D., Remoli, M. E., Julkunen, I., Cella, M., Lande, R. & Uzé, G. ( 2004; ). Viral infection and Toll-like receptor agonists induce a differential expression of type I and λ interferons in human plasmacytoid and monocyte-derived dendritic cells. Eur J Immunol 34, 796–805.[CrossRef]
    [Google Scholar]
  5. Der, S. D., Zhou, A., Williams, B. R. G. & Silverman, R. H. ( 1998; ). Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays. Proc Natl Acad Sci U S A 95, 15623–15628.[CrossRef]
    [Google Scholar]
  6. Duerst, R. J. & Morrison, L. A. ( 2003; ). Innate immunity to herpes simplex virus type 2. Viral Immunol 16, 475–490.[CrossRef]
    [Google Scholar]
  7. Eidson, K. M., Hobbs, W. E., Manning, B. J., Carlson, P. & DeLuca, N. A. ( 2002; ). Expression of herpes simplex virus ICP0 inhibits the induction of interferon-stimulated genes by viral infection. J Virol 76, 2180–2191.[CrossRef]
    [Google Scholar]
  8. Hardwicke, M. A. & Sandri-Goldin, R. M. ( 1994; ). The herpes simplex virus regulatory protein ICP27 contributes to the decrease in cellular mRNA levels during infection. J Virol 68, 4797–4810.
    [Google Scholar]
  9. Hardy, W. R. & Sandri-Goldin, R. M. ( 1994; ). Herpes simplex virus inhibits host cell splicing, and regulatory protein ICP27 is required for this effect. J Virol 68, 7790–7799.
    [Google Scholar]
  10. Härle, P., Cull, V., Agbaga, M.-P., Silverman, R., Williams, B. R. G., James, C. & Carr, D. J. J. ( 2002a; ). Differential effect of murine alpha/beta interferon transgenes on antagonization of herpes simplex virus type 1 replication. J Virol 76, 6558–6567.[CrossRef]
    [Google Scholar]
  11. Härle, P., Sainz, B., Jr, Carr, D. J. J. & Halford, W. P. ( 2002b; ). The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus to interferon-α/β. Virology 293, 295–304.[CrossRef]
    [Google Scholar]
  12. He, B., Gross, M. & Roizman, B. ( 1997; ). The γ 134.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc Natl Acad Sci U S A 94, 843–848.[CrossRef]
    [Google Scholar]
  13. Jean, S., LeVan, K. M., Song, B., Levine, M. & Knipe, D. M. ( 2001; ). Herpes simplex virus 1 ICP27 is required for transcription of two viral late (γ2) genes in infected cells. Virology 283, 273–284.[CrossRef]
    [Google Scholar]
  14. Klotzbücher, A., Mittnacht, S., Kirchner, H. & Jacobsen, H. ( 1990; ). Different effects of IFNγ and IFNα/β on “immediate early” gene expression of HSV-1. Virology 179, 487–491.[CrossRef]
    [Google Scholar]
  15. Kodukula, P., Liu, T., Van Rooijen, N., Jager, M. J. & Hendricks, R. L. ( 1999; ). Macrophage control of herpes simplex virus type 1 replication in the peripheral nervous system. J Immunol 162, 2895–2905.
    [Google Scholar]
  16. Kotenko, S. V., Gallagher, G., Baurin, V. V. & 7 other authors ( 2003; ). IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4, 69–77.
    [Google Scholar]
  17. Krug, A., Luker, G. D., Barchet, W., Leib, D. A., Akira, S. & Colonna, M. ( 2004; ). Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 103, 1433–1437.
    [Google Scholar]
  18. Kurt-Jones, E. A., Chan, M., Zhou, S., Wang, J., Reed, G., Bronson, R., Arnold, M. M., Knipe, D. M. & Finberg, R. W. ( 2004; ). Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci U S A 101, 1315–1320.[CrossRef]
    [Google Scholar]
  19. Lin, R., Noyce, R. S., Collins, S. E., Everett, R. D. & Mossman, K. L. ( 2004; ). The herpes simplex virus ICP0 RING finger domain inhibits IRF3- and IRF7-mediated activation of interferon-stimulated genes. J Virol 78, 1675–1684.[CrossRef]
    [Google Scholar]
  20. Lucey, D. R., Clerici, M. & Shearer, G. M. ( 1996; ). Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev 9, 532–562.
    [Google Scholar]
  21. Lund, J., Sato, A., Akira, S., Medzhitov, R. & Iwasaki, A. ( 2003; ). Toll-like receptor 9-mediated recognition of herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med 198, 513–520.[CrossRef]
    [Google Scholar]
  22. Malmgaard, L., Melchjorsen, J., Bowie, A. G., Mogensen, S. C. & Paludan, S. R. ( 2004; ). Viral activation of macrophages through TLR-dependent and -independent pathways. J Immunol 173, 6890–6898.[CrossRef]
    [Google Scholar]
  23. Marié, I., Durbin, J. E. & Levy, D. E. ( 1998; ). Differential viral induction of distinct interferon-α genes by positive feedback through interferon regulatory factor-7. EMBO J 17, 6660–6669.[CrossRef]
    [Google Scholar]
  24. Matikainen, S., Pirhonen, J., Miettinen, M., Lehtonen, A., Govenius-Vintola, C., Sareneva, T. & Julkunen, I. ( 2000; ). Influenza A and Sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages. Virology 276, 138–147.[CrossRef]
    [Google Scholar]
  25. McCarthy, A. M., McMahan, L. & Schaffer, P. A. ( 1989; ). Herpes simplex virus type 1 ICP27 deletion mutants exhibit altered patterns of transcription and are DNA deficient. J Virol 63, 18–27.
    [Google Scholar]
  26. 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]
  27. Melchjorsen, J., Sørensen, L. N. & Paludan, S. R. ( 2003; ). Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function. J Leukoc Biol 74, 331–343.[CrossRef]
    [Google Scholar]
  28. Melroe, G. T., DeLuca, N. A. & Knipe, D. M. ( 2004; ). Herpes simplex virus 1 has multiple mechanisms for blocking virus-induced interferon production. J Virol 78, 8411–8420.[CrossRef]
    [Google Scholar]
  29. Miettinen, M., Matikainen, S., Vuopio-Varkila, J., Pirhonen, J., Varkila, K., Kurimoto, M. & Julkunen, I. ( 1998; ). Lactobacilli and streptococci induce interleukin-12 (IL-12), IL-18, and gamma interferon production in human peripheral blood mononuclear cells. Infect Immun 66, 6058–6062.
    [Google Scholar]
  30. Mogensen, T. H. & Paludan, S. R. ( 2001; ). Molecular pathways in virus-induced cytokine production. Microbiol Mol Biol Rev 65, 131–150.[CrossRef]
    [Google Scholar]
  31. Mogensen, T. H., Melchjorsen, J., Malmgaard, L., Casola, A. & Paludan, S. R. ( 2004; ). Suppression of proinflammatory cytokine expression by herpes simplex virus type 1. J Virol 78, 5883–5890.[CrossRef]
    [Google Scholar]
  32. Mossman, K. L., Saffran, H. A. & Smiley, J. R. ( 2000; ). Herpes simplex virus ICP0 mutants are hypersensitive to interferon. J Virol 74, 2052–2056.[CrossRef]
    [Google Scholar]
  33. Nemeroff, M. E., Barabino, S. M. L., Li, Y., Keller, W. & Krug, R. M. ( 1998; ). Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3′ end formation of cellular pre-mRNAs. Mol Cell 1, 991–1000.[CrossRef]
    [Google Scholar]
  34. Oberman, F. & Panet, A. ( 1988; ). Inhibition of transcription of herpes simplex virus immediate early genes in interferon-treated human cells. J Gen Virol 69, 1167–1177.[CrossRef]
    [Google Scholar]
  35. Paludan, S. R. ( 2001; ). Requirements for the induction of interleukine-6 by herpes simplex virus-infected leukocytes. J Virol 75, 8008–8015.[CrossRef]
    [Google Scholar]
  36. Paludan, S. R. & Mogensen, S. C. ( 2001; ). Virus-cell interactions regulating induction of tumor necrosis factor α production in macrophages infected with herpes simplex virus. J Virol 75, 10170–10178.[CrossRef]
    [Google Scholar]
  37. Paludan, S. R., Melchjorsen, J., Malmgaard, L. & Mogensen, S. C. ( 2002; ). Expression of genes for cytokines and cytokine-related functions in leukocytes infected with Herpes simplex virus: comparison between resistant and susceptible mouse strains. Eur Cytokine Netw 13, 306–316.
    [Google Scholar]
  38. Pirhonen, J., Sareneva, T., Kurimoto, M., Julkunen, I. & Matikainen, S. ( 1999; ). Virus infection activates IL-1β and IL-18 production in human macrophages by a caspase-1-dependent pathway. J Immunol 162, 7322–7329.
    [Google Scholar]
  39. Poppers, J., Mulvey, M., Khoo, D. & Mohr, I. ( 2000; ). Inhibition of PKR activation by the proline-rich RNA binding domain of the herpes simplex virus type 1 Us11 protein. J Virol 74, 11215–11221.[CrossRef]
    [Google Scholar]
  40. Rice, S. A. & Knipe, D. M. ( 1990; ). Genetic evidence for two distinct transactivation functions of the herpes simplex virus alpha protein ICP27. J Virol 64, 1704–1715.
    [Google Scholar]
  41. Robek, M. D., Boyd, B. S. & Chisari, F. V. ( 2005; ). Lambda interferon inhibits hepatitis B and C virus replication. J Virol 79, 3851–3854.[CrossRef]
    [Google Scholar]
  42. Romagnani, S. ( 1997; ). The Th1/Th2 paradigm. Immunol Today 18, 263–266.
    [Google Scholar]
  43. Sacks, W. R., Greene, C. C., Aschman, D. P. & Schaffer, P. A. ( 1985; ). Herpes simplex virus type 1 ICP27 is an essential regulatory protein. J Virol 55, 796–805.
    [Google Scholar]
  44. Sen, G. C. ( 2001; ). Viruses and interferons. Annu Rev Microbiol 55, 255–281.[CrossRef]
    [Google Scholar]
  45. Shepard, A. A. & DeLuca, N. A. ( 1991; ). Activities of heterodimers composed of DNA-binding- and transactivation-deficient subunits of the herpes simplex virus regulatory protein ICP4. J Virol 65, 299–307.
    [Google Scholar]
  46. Sheppard, P., Kindsvogel, W., Xu, W. & 23 other authors ( 2003; ). IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 4, 63–68.[CrossRef]
    [Google Scholar]
  47. Sirén, J., Pirhonen, J., Julkunen, I. & Matikainen, S. ( 2005; ). IFN-α regulates TLR-dependent gene expression of IFN-α, IFN-β, IL-28, and IL-29. J Immunol 174, 1932–1937.[CrossRef]
    [Google Scholar]
  48. Song, B., Yeh, K.-C., Liu, J. & Knipe, D. M. ( 2001; ). Herpes simplex virus gene products required for viral inhibition of expression of G1-phase functions. Virology 290, 320–328.[CrossRef]
    [Google Scholar]
  49. Spencer, C. A., Dahmus, M. E. & Rice, S. A. ( 1997; ). Repression of host RNA polymerase II transcription by herpes simplex virus type 1. J Virol 71, 2031–2040.
    [Google Scholar]
  50. Stingley, S. W., Garcia Ramirez, J. J., Aguilar, S. A., Simmen, K., Sandri-Goldin, R. M., Ghazal, P. & Wagner, E. K. ( 2000; ). Global analysis of herpes simplex virus type 1 transcription using an oligonucleotide-based DNA microarray. J Virol 74, 9916–9927.[CrossRef]
    [Google Scholar]
  51. Stow, N. D. & Stow, E. C. ( 1986; ). Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate early polypeptide Vmw110. J Gen Virol 67, 2571–2585.[CrossRef]
    [Google Scholar]
  52. Uprichard, S. L. & Knipe, D. M. ( 1996; ). Herpes simplex ICP27 mutant viruses exhibit reduced expression of specific DNA replication genes. J Virol 70, 1969–1980.
    [Google Scholar]
  53. Veckman, V., Miettinen, M., Matikainen, S., Lande, R., Giacomini, E., Coccia, E. M. & Julkunen, I. ( 2003; ). Lactobacilli and streptococci induce inflammatory chemokine production in human macrophages that stimulates Th1 cell chemotaxis. J Leukoc Biol 74, 395–402.[CrossRef]
    [Google Scholar]
  54. Veckman, V., Miettinen, M., Pirhonen, J., Sirén, J., Matikainen, S. & Julkunen, I. ( 2004; ). Streptococcus pyogenes and Lactobacillus rhamnosus differentially induce maturation and production of Th1-type cytokines and chemokines in human monocyte-derived dendritic cells. J Leukoc Biol 75, 764–771.
    [Google Scholar]
  55. Whitley, R. J. & Roizman, B. ( 2001; ). Herpes simplex virus infections. Lancet 357, 1513–1518.[CrossRef]
    [Google Scholar]
  56. Zhao, X., Deak, E., Soderberg, K., Linehan, M., Spezzano, D., Zhu, J., Knipe, D. M. & Iwasaki, A. ( 2003; ). Vaginal submucosal dendritic cells, but not Langerhans cells, induce protective Th1 responses to herpes simplex virus-2. J Exp Med 197, 153–162.[CrossRef]
    [Google Scholar]
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