1887

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Volume 89, Issue 6

Protein tyrosine phosphatase-H2 from a polydnavirus induces apoptosis of insect cells Free

Abstract

The family is a large group of immunosuppressive insect viruses that are symbiotically associated with parasitoid wasps. The polydnavirus bracovirus (MdBV) causes several alterations that disable the cellular and humoral immune defences of host insects, including apoptosis of the primary phagocytic population of circulating immune cells (haemocytes), called granulocytes. Here, we show that MdBV infection causes granulocytes in the lepidopteran to apoptose. An expression screen conducted in the 21 cell line identified the MdBV gene as an apoptosis inducer, as indicated by cell fragmentation, annexin V binding, mitochondrial membrane depolarization and caspase activation. PTP-H2 is a classical protein tyrosine phosphatase that has been shown previously to function as an inhibitor of phagocytosis. PTP-H2-mediated death of Sf-21 cells was blocked by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-(-methyl) Asp-fluoromethylketone (Z-VAD-FMK), but cells maintained in this inhibitor still exhibited a suppressed phagocytic response. Mutagenesis experiments indicated that the essential catalytic cysteine residue required for the phosphatase activity of PTP-H2 was required for apoptotic activity in Sf-21 cells. Loss of adhesion was insufficient to stimulate apoptosis of Sf-21 cells. PTP-H2 expression, however, did significantly reduce proliferation of Sf-21 cells, which could contribute to the apoptotic activity of this viral gene. Overall, our results indicate that specific genes expressed by MdBV induce apoptosis of certain insect cells and that this activity contributes to immunosuppression of hosts.

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2008-06-01
2024-04-19
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References

  1. Abdelwahid E., Yokokura T., Krieser R. J., Balasundaram S., Fowle W. H., White K. 2007; Mitochondrial disruption in Drosophila apoptosis. Dev Cell 12:793–806 [CrossRef]
     [Google Scholar]
  2. Beck M., Strand M. R. 2003; RNA interference silences Microplitis demolitor bracovirus genes and implicates glc1.8 in disruption of adhesion in infected host cells. Virology 314:521–535 [CrossRef]
     [Google Scholar]
  3. Beck M., Strand M. R. 2005; Glc1.8 from Microplitis demolitor bracovirus induces a loss of adhesion and phagocytosis in insect High Five and S2 cells. J Virol 79:1861–1870 [CrossRef]
     [Google Scholar]
  4. Beck M. H., Strand M. R. 2007; A novel polydnavirus protein inhibits the insect prophenoloxidase activation pathway. Proc Natl Acad Sci U S A 104:19267–19272 [CrossRef]
     [Google Scholar]
  5. Beck M. H., Inman R. B., Strand M. R. 2007; Microplitis demolitor bracovirus genome segments vary in abundance and are individually packaged in virions. Virology 359:179–189 [CrossRef]
     [Google Scholar]
  6. Bruckner S., Rhamouni S., Tautz L., Denault J. B., Alonso A., Becattini B., Salvesen G. S., Mustelin T. 2005; Yersinia phosphatase induces mitochondrially dependent apoptosis of T cells. J Biol Chem 280:10388–10394 [CrossRef]
     [Google Scholar]
  7. Clem R. J., Miller L. K. 1993; Apoptosis reduces both the in vitro replication and the in vivo infectivity of a baculovirus. J Virol 67:3730–3738
     [Google Scholar]
  8. Clem R. J., Fechheimer M., Miller L. K. 1991; Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science 254:1388–1390 [CrossRef]
     [Google Scholar]
  9. Clem R. J., Robson M., Miller L. K. 1994; Influence of infection route on the infectivity of baculovirus mutants lacking the apoptosis-inhibiting gene p35 and the adjacent gene p94. J Virol 68:6759–6762
     [Google Scholar]
  10. Danial N. N., Korsmeyer S. J. 2004; Cell death: critical control points. Cell 116:205–219 [CrossRef]
     [Google Scholar]
  11. Dupuy C., Huguet E., Drezen J.-M. 2006; Unfolding the evolutionary history of polydnaviruses. Virus Res 117:81–89 [CrossRef]
     [Google Scholar]
  12. Gardiner E. M., Strand M. R. 2000; Hematopoiesis in larval Pseudoplusia includens and Spodoptera frugiperda . Arch Insect Biochem Physiol 43:147–164 [CrossRef]
     [Google Scholar]
  13. Gilmore A. P. 2005; Anoikis. Cell Death Differ 12:Suppl. 21473–1477 [CrossRef]
     [Google Scholar]
  14. Gorman A. M., Samali A., McGowan A. J., Cotter T. G. 1997; Use of flow cytometry techniques in studying mechanisms of apoptosis in leukemic cells. Cytometry 29:97–105 [CrossRef]
     [Google Scholar]
  15. Gu F., Nguyen D. T., Stuible M., Dube N., Tremblay M. L., Chevet E. 2004; Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic reticulum stress. J Biol Chem 279:49689–49693 [CrossRef]
     [Google Scholar]
  16. Halle M., Liu Y. C., Hardy S., Theberge J. F., Blanchetot C., Bourdeau A., Meng T. C., Tremblay M. L. 2007; Caspase-3 regulates catalytic activity and scaffolding functions of the protein tyrosine phosphatase PEST, a novel modulator of the apoptotic response. Mol Cell Biol 27:1172–1190 [CrossRef]
     [Google Scholar]
  17. Hershberger P. A., LaCount D. J., Friesen P. D. 1994; The apoptotic suppressor P35 is required early during baculovirus replication and is targeted to the cytosol of infected cells. J Virol 68:3467–3477
     [Google Scholar]
  18. Huang Q., Deveraux Q. L., Maeda S., Salvesen G. S., Stennicke H. R., Hammock B. D., Reed J. C. 2000; Evolutionary conservation of apoptosis mechanisms: lepidopteran and baculoviral inhibitor of apoptosis proteins are inhibitors of mammalian caspase-9. Proc Natl Acad Sci U S A 97:1427–1432 [CrossRef]
     [Google Scholar]
  19. Ibrahim A. M., Choi J. Y., Je Y. H., Kim Y. 2007; Protein tyrosine phosphatases encoded in Cotesia plutellae bracovirus: sequence analysis, expression profile, and a possible biological role in host immunosuppression. Dev Comp Immunol 31:978–990 [CrossRef]
     [Google Scholar]
  20. Kroemer J. A., Webb B. A. 2004; Polydnavirus genes and genomes: emerging gene families and new insights into polydnavirus replication. Annu Rev Entomol 49:431–456 [CrossRef]
     [Google Scholar]
  21. Kuranaga E., Miura M. 2007; Nonapoptotic functions of caspases: caspases as regulatory molecules for immunity and cell-fate determination. Trends Cell Biol 17:135–144 [CrossRef]
     [Google Scholar]
  22. Lapointe R., Wilson R., Vilaplana L., O'Reilly D. R., Falabella P., Douris V., Bernier-Cardou M., Pennacchio F., Iatrou K. other authors 2005; Expression of a Toxoneuron nigriceps polydnavirus-encoded protein causes apoptosis-like programmed cell death in lepidopteran insect cells. J Gen Virol 86:963–971 [CrossRef]
     [Google Scholar]
  23. Lavine M. D., Strand M. R. 2003; Haemocytes from Pseudoplusia includens express multiple α and β integrin subunits. Insect Mol Biol 12:441–452 [CrossRef]
     [Google Scholar]
  24. Li K., Li Y., Shelton J. M., Richardson J. A., Spencer E., Chen Z. J., Wang X., Williams R. S. 2000; Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Cell 101:389–399 [CrossRef]
     [Google Scholar]
  25. Muro I., Hay B. A., Clem R. J. 2002; The Drosophila DIAP1 protein is required to prevent accumulation of a continuously generated, processed form of the apical caspase DRONC. J Biol Chem 277:49644–49650 [CrossRef]
     [Google Scholar]
  26. Nardi J. B., Pilas B., Bee C. M., Zhuang S., Garsha K., Kanost M. R. 2006; Neuroglian-positive plasmatocytes of Manduca sexta and the initiation of hemocyte attachment to foreign surfaces. Dev Comp Immunol 30:447–462 [CrossRef]
     [Google Scholar]
  27. Olson M. R., Holley C. L., Gan E. C., Colon-Ramos D. A., Kaplan B., Kornbluth S. 2003; A GH3-like domain in reaper is required for mitochondrial localization and induction of IAP degradation. J Biol Chem 278:44758–44768 [CrossRef]
     [Google Scholar]
  28. Pech L. L., Strand M. R. 1996; Granular cells are required for encapsulation of foreign targets by insect haemocytes. J Cell Sci 109:2053–2060
     [Google Scholar]
  29. Pech L. L., Trudeau D., Strand M. R. 1994; Separation and behavior in vitro of hemocytes from the moth, Pseudoplusia includens . Cell Tissue Res 277:159–167 [CrossRef]
     [Google Scholar]
  30. Pennacchio F., Strand M. R. 2006; Evolution of developmental strategies in parasitic Hymenoptera. Annu Rev Entomol 51:233–258 [CrossRef]
     [Google Scholar]
  31. Pruijssers A. J., Strand M. R. 2007; PTP-H2 and PTP-H3 from Microplitis demolitor bracovirus localize to focal adhesions and are antiphagocytic in insect immune cells. J Virol 81:1209–1219 [CrossRef]
     [Google Scholar]
  32. Schmidt O., Theopold U., Strand M. 2001; Innate immunity and its evasion and suppression by hymenopteran endoparasitoids. Bioessays 23:344–351 [CrossRef]
     [Google Scholar]
  33. Strand M. R. 1994; Microplitis demolitor polydnavirus infects and expresses in specific morphotypes of Pseudoplusia includens haemocytes. J Gen Virol 75:3007–3020 [CrossRef]
     [Google Scholar]
  34. Strand M. R. 2008; Insect hemocytes and their role in immunity. In Insect Immunology pp 25–48Edited by Beckage N. E. San Diego, CA: Elsevier;
     [Google Scholar]
  35. Strand M. R., Noda T. 1991; Alterations in the haemocytes of Pseudoplusia includens after parasitism by Microplitis demolitor . J Insect Physiol 37:839–850 [CrossRef]
     [Google Scholar]
  36. Strand M. R., Pech L. L. 1995a; Immunological basis for compatibility in parasitoid-host relationships. Annu Rev Entomol 40:31–56 [CrossRef]
     [Google Scholar]
  37. Strand M. R., Pech L. L. 1995b; Microplitis demolitor polydnavirus induces apoptosis of a specific haemocyte morphotype in Pseudoplusia includens . J Gen Virol 76:283–291 [CrossRef]
     [Google Scholar]
  38. Strand M. R., McKenzie D. I., Grassl V., Dover B. A., Aiken J. M. 1992; Persistence and expression of Microplitis demolitor polydnavirus in Pseudoplusia includens . J Gen Virol 73:1627–1635 [CrossRef]
     [Google Scholar]
  39. Strand M. R., Witherell R. A., Trudeau D. 1997; Two Microplitis demolitor polydnavirus mRNAs expressed in hemocytes of Pseudoplusia includens contain a common cysteine-rich domain. J Virol 71:2146–2156
     [Google Scholar]
  40. Strand M. R., Beck M. H., Lavine M. D., Clark K. D. 2006; Microplitis demolitor bracovirus inhibits phagocytosis by hemocytes from Pseudoplusia includens . Arch Insect Biochem Physiol 61:134–145 [CrossRef]
     [Google Scholar]
  41. Takada T., Noguchi T., Inagaki K., Hosooka T., Fukunaga K., Yamao T., Ogawa W., Matozaki T., Kasuga M. 2002; Induction of apoptosis by stomach cancer-associated protein-tyrosine phosphatase-1. J Biol Chem 277:34359–34366 [CrossRef]
     [Google Scholar]
  42. Thoetkiattikul H., Beck M. H., Strand M. R. 2005; Inhibitor κ B-like proteins from a polydnavirus inhibit NF- κ B activation and suppress the insect immune response. Proc Natl Acad Sci U S A 102:11426–11431 [CrossRef]
     [Google Scholar]
  43. Trudeau D., Strand M. R. 1998; A limited role in parasitism for Microplitis demolitor polydnavirus. J Insect Physiol 44:795–805 [CrossRef]
     [Google Scholar]
  44. Trudeau D., Witherell R. A., Strand M. R. 2000; Characterization of two novel Microplitis demolitor polydnavirus mRNAs expressed in Pseudoplusia includens haemocytes. J Gen Virol 81:3049–3058
     [Google Scholar]
  45. Webb B. A., Strand M. R. 2005; The biology and genomics of polydnaviruses. In Comprehensive Molecular Insect Science . pp 260–323Edited by Gilbert I., Iatrou K., Gill. San Diego, CA: Elsevier;
  46. Webb B. A., Strand M. R., Dickey S. E., Beck M. H., Hilgarth R. S., Barney W. E., Kadash K., Kroemer J. A., Lindstrom K. G. other authors 2006; Polydnavirus genomes reflect their dual roles as mutualists and pathogens. Virology 347:160–174 [CrossRef]
     [Google Scholar]
  47. Wells B. S., Yoshida E., Johnston L. A. 2006; Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity. Curr Biol 16:1606–1615 [CrossRef]
     [Google Scholar]
  48. Woo J. H., Kim Y. H., Choi Y. J., Kim D. G., Lee K. S., Bae J. H., Min D. S., Chang J. S., Jeong Y. J. other authors 2003; Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis 24:1199–1208 [CrossRef]
     [Google Scholar]
  49. Yousefi S., Simon H. U. 2003; SHP-1: a regulator of neutrophil apoptosis. Semin Immunol 15:195–199 [CrossRef]
     [Google Scholar]
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Protein tyrosine phosphatase-H2 from a polydnavirus induces apoptosis of insect cells
J. Gen. Virol. 89, 1411 (2008); https://doi.org/10.1099/vir.0.2008/000307-0
/content/journal/jgv/10.1099/vir.0.2008/000307-0
/content/journal/jgv/10.1099/vir.0.2008/000307-0
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