Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1991 Jun;65(6):3151–3160. doi: 10.1128/jvi.65.6.3151-3160.1991

Immediate-early gene expression is sufficient for induction of natural killer cell-mediated lysis of herpes simplex virus type 1-infected fibroblasts.

P Fitzgerald-Bocarsly 1, D M Howell 1, L Pettera 1, S Tehrani 1, C Lopez 1
PMCID: PMC240971  PMID: 1709697

Abstract

Herpes simplex virus type 1 (HSV-1)-infected human fibroblast (HSV-FS) targets are susceptible to lysis by natural killer (NK) cells, whereas uninfected FS are resistant to lysis. Studies were undertaken to determine the mechanism of this preferential susceptibility. HSV-FS were not intrinsically less stable than FS, as determined by a 51Cr release assay under hypotonic shock in the presence of rat granule cytolysin and by sensitivity to anti-human leukocyte antigen class I antibody plus complement. Single-cell assays in agarose demonstrated that although similar numbers of large granular lymphocytes bound to the HSV-FS and FS targets, the conjugates with HSV-FS were lysed at a much higher frequency than those with FS. These results suggested that both targets are bound by the NK cells but only the HSV-FS were able to trigger lysis. The requirement for active virus expression was demonstrated by failure of emetine-treated HSV-FS targets or targets infected with UV-inactivated HSV to be lysed by NK effectors. To evaluate the role of viral glycoproteins in conferring susceptibility to lysis, Fab were prepared from HSV-1-seropositive sera; these Fab were unable to block lysis of the HSV-FS. Furthermore, incubation in phosphonoacetic acid failed to reduce NK(HSV-FS) activity despite sharp reductions in viral glycoprotein synthesis. Finally, targets infected with tsLB2 at the nonpermissive temperature were lysed as well as or better than targets infected with wild-type virus, indicating that HSV immediate-early gene product expression is sufficient for conferring susceptibility to lysis. We conclude that expression of nonstructural viral proteins or virally induced cellular gene products early in the course of infection rather than structural glycoproteins is required for NK lysis of HSV-FS targets.

Full text

PDF
3151

Images in this article

3155Image
on p.3155
3156Image
on p.3156
3157Image
on p.3157

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abb J., Abb H., Deinhardt F. Phenotype of human alpha-interferon producing leucocytes identified by monoclonal antibodies. Clin Exp Immunol. 1983 Apr;52(1):179–184. [PMC free article] [PubMed] [Google Scholar]
  2. Bandyopadhyay S., Perussia B., Trinchieri G., Miller D. S., Starr S. E. Requirement for HLA-DR+ accessory cells in natural killing of cytomegalovirus-infected fibroblasts. J Exp Med. 1986 Jul 1;164(1):180–195. doi: 10.1084/jem.164.1.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bishop G. A., Glorioso J. C., Schwartz S. A. Relationship between expression of herpes simplex virus glycoproteins and susceptibility of target cells to human natural killer activity. J Exp Med. 1983 May 1;157(5):1544–1561. doi: 10.1084/jem.157.5.1544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bishop G. A., Glorioso J. C., Schwartz S. A. Role of interferon in human natural killer activity against target cells infected with HSV-1. J Immunol. 1983 Oct;131(4):1849–1853. [PubMed] [Google Scholar]
  5. Bishop G. A., Kümel G., Schwartz S. A., Glorioso J. C. Specificity of human natural killer cells in limiting dilution culture for determinants of herpes simplex virus type 1 glycoproteins. J Virol. 1986 Jan;57(1):294–300. doi: 10.1128/jvi.57.1.294-300.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bishop G. A., Marlin S. D., Schwartz S. A., Glorioso J. C. Human natural killer cell recognition of herpes simplex virus type 1 glycoproteins: specificity analysis with the use of monoclonal antibodies and antigenic variants. J Immunol. 1984 Oct;133(4):2206–2214. [PubMed] [Google Scholar]
  7. Borysiewicz L. K., Graham S., Sissons J. G. Human natural killer cell lysis of virus-infected cells. Relationship to expression of the transferrin receptor. Eur J Immunol. 1986 Apr;16(4):405–411. doi: 10.1002/eji.1830160416. [DOI] [PubMed] [Google Scholar]
  8. Borysiewicz L. K., Rodgers B., Morris S., Graham S., Sissons J. G. Lysis of human cytomegalovirus infected fibroblasts by natural killer cells: demonstration of an interferon-independent component requiring expression of early viral proteins and characterization of effector cells. J Immunol. 1985 Apr;134(4):2695–2701. [PubMed] [Google Scholar]
  9. Brooks C. G., Wayner E. A., Webb P. J., Gray J. D., Kenwrick S., Baldwin R. W. The specificity of rat natural killer cells and cytotoxic macrophages on solid tumor-derived target cells and selected variants. J Immunol. 1981 Dec;127(6):2477–2483. [PubMed] [Google Scholar]
  10. Bukowski J. F., Warner J. F., Dennert G., Welsh R. M. Adoptive transfer studies demonstrating the antiviral effect of natural killer cells in vivo. J Exp Med. 1985 Jan 1;161(1):40–52. doi: 10.1084/jem.161.1.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cook C. G., Splitter G. A. Characterization of bovine mononuclear cell populations with natural cytolytic activity against bovine herpesvirus 1-infected cells. Cell Immunol. 1989 Apr 15;120(1):240–249. doi: 10.1016/0008-8749(89)90191-3. [DOI] [PubMed] [Google Scholar]
  12. Cook J. L., May D. L., Lewis A. M., Jr, Walker T. A. Adenovirus E1A gene induction of susceptibility to lysis by natural killer cells and activated macrophages in infected rodent cells. J Virol. 1987 Nov;61(11):3510–3520. doi: 10.1128/jvi.61.11.3510-3520.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Estridge J. K., Kemp L. M., La Thangue N. B., Mann B. S., Tyms A. S., Latchman D. S. The herpes simplex virus type 1 immediate-early protein ICP27 is obligately required for the accumulation of a cellular protein during viral infection. Virology. 1989 Jan;168(1):67–72. doi: 10.1016/0042-6822(89)90404-2. [DOI] [PubMed] [Google Scholar]
  14. Feldman M., Fitzgerald-Bocarsly P. Sequential enrichment and immunocytochemical visualization of human interferon-alpha-producing cells. J Interferon Res. 1990 Aug;10(4):435–446. doi: 10.1089/jir.1990.10.435. [DOI] [PubMed] [Google Scholar]
  15. Fitzgerald-Bocarsly P., Feldman M., Curl S., Schnell J., Denny T. Positively selected Leu-11a (CD16+) cells require the presence of accessory cells or factors for the lysis of herpes simplex virus-infected fibroblasts but not herpes simplex virus-infected Raji. J Immunol. 1989 Aug 15;143(4):1318–1326. [PubMed] [Google Scholar]
  16. Fitzgerald-Bocarsly P., Feldman M., Mendelsohn M., Curl S., Lopez C. Human mononuclear cells which produce interferon-alpha during NK(HSV-FS) assays are HLA-DR positive cells distinct from cytolytic natural killer effectors. J Leukoc Biol. 1988 Apr;43(4):323–334. doi: 10.1002/jlb.43.4.323. [DOI] [PubMed] [Google Scholar]
  17. Fitzgerald P. A., Mendelsohn M., Lopez C. Human natural killer cells limit replication of herpes simplex virus type 1 in vitro. J Immunol. 1985 Apr;134(4):2666–2672. [PubMed] [Google Scholar]
  18. Fitzgerald P. A., von Wussow P., Lopez C. Role of interferon in natural kill of HSV-1-infected fibroblasts. J Immunol. 1982 Aug;129(2):819–823. [PubMed] [Google Scholar]
  19. Gelman I. H., Silverstein S. Identification of immediate early genes from herpes simplex virus that transactivate the virus thymidine kinase gene. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5265–5269. doi: 10.1073/pnas.82.16.5265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gobl A. E., Funa K., Alm G. V. Different induction patterns of mRNA for IFN-alpha and -beta in human mononuclear leukocytes after in vitro stimulation with herpes simplex virus-infected fibroblasts and Sendai virus. J Immunol. 1988 May 15;140(10):3605–3609. [PubMed] [Google Scholar]
  21. Goding J. W. Use of staphylococcal protein A as an immunological reagent. J Immunol Methods. 1978;20:241–253. doi: 10.1016/0022-1759(78)90259-4. [DOI] [PubMed] [Google Scholar]
  22. Grimm E., Bonavida B. Mechanism of cell-mediated cytotoxicity at the single cell level. I. Estimation of cytotoxic T lymphocyte frequency and relative lytic efficiency. J Immunol. 1979 Dec;123(6):2861–2869. [PubMed] [Google Scholar]
  23. Halliburton I. W., Randall R. E., Killington R. A., Watson D. H. Some properties of recombinants between type 1 and type 2 herpes simplex viruses. J Gen Virol. 1977 Sep;36(3):471–484. doi: 10.1099/0022-1317-36-3-471. [DOI] [PubMed] [Google Scholar]
  24. Henkart P. A., Millard P. J., Reynolds C. W., Henkart M. P. Cytolytic activity of purified cytoplasmic granules from cytotoxic rat large granular lymphocyte tumors. J Exp Med. 1984 Jul 1;160(1):75–93. doi: 10.1084/jem.160.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Honess R. W., Watson D. H. Herpes simplex virus resistance and sensitivity to phosphonoacetic acid. J Virol. 1977 Feb;21(2):584–600. doi: 10.1128/jvi.21.2.584-600.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kwong A. D., Kruper J. A., Frenkel N. Herpes simplex virus virion host shutoff function. J Virol. 1988 Mar;62(3):912–921. doi: 10.1128/jvi.62.3.912-921.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lebon P. Inhibition of herpes simplex virus type 1-induced interferon synthesis by monoclonal antibodies against viral glycoprotein D and by lysosomotropic drugs. J Gen Virol. 1985 Dec;66(Pt 12):2781–2786. doi: 10.1099/0022-1317-66-12-2781. [DOI] [PubMed] [Google Scholar]
  28. Leibson P. J., Hunter-Laszlo M., Hayward A. R. Inhibition of herpes simplex virus type 1 replication in fibroblast cultures by human blood mononuclear cells. J Virol. 1986 Mar;57(3):976–982. doi: 10.1128/jvi.57.3.976-982.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. López-Guerrero J. A., Alarcón B., Fresno M. Mechanism of recognition of herpes simplex virus type 1-infected cells by natural killer cells. J Gen Virol. 1988 Nov;69(Pt 11):2859–2868. doi: 10.1099/0022-1317-69-11-2859. [DOI] [PubMed] [Google Scholar]
  30. Moller J. R., Rager-Zisman B., Quan P. C., Schattner A., Panush D., Rose J. K., Bloom B. R. Natural killer cell recognition of target cells expressing different antigens of vesicular stomatitis virus. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2456–2459. doi: 10.1073/pnas.82.8.2456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Oh S. H., Bandyopadhyay S., Miller D. S., Starr S. E. Cooperation between CD16(Leu-11b)+ NK cells and HLA-DR+ cells in natural killing of herpesvirus-infected fibroblasts. J Immunol. 1987 Oct 15;139(8):2799–2802. [PubMed] [Google Scholar]
  32. Perussia B., Fanning V., Trinchieri G. A leukocyte subset bearing HLA-DR antigens is responsible for in vitro alpha interferon production in response to viruses. Nat Immun Cell Growth Regul. 1985;4(3):120–137. [PubMed] [Google Scholar]
  33. Pross H. F., Baines M. G., Rubin P., Shragge P., Patterson M. S. Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity. J Clin Immunol. 1981 Jan;1(1):51–63. doi: 10.1007/BF00915477. [DOI] [PubMed] [Google Scholar]
  34. Rönnblom L., Alm G. V. Limiting dilution analysis of human peripheral blood mononuclear leukocytes that react to human amnion cells and protect these against viral challenge. Eur J Immunol. 1982 May;12(5):437–441. doi: 10.1002/eji.1830120515. [DOI] [PubMed] [Google Scholar]
  35. Schattner A., Rager-Zisman B. Lysis by natural killer cells requires viral replication and glycoprotein expression. Immunol Lett. 1986 Oct 15;13(5):261–268. doi: 10.1016/0165-2478(86)90111-2. [DOI] [PubMed] [Google Scholar]
  36. Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187–376. doi: 10.1016/S0065-2776(08)60664-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Welsh R. M. Regulation of virus infections by natural killer cells. A review. Nat Immun Cell Growth Regul. 1986;5(4):169–199. [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES