1887

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Volume 91, Issue 11

The classical swine fever virus N-terminal protease N binds to cellular HAX-1 Free

Abstract

The positive-stranded RNA genome of classical swine fever virus (CSFV) encodes 12 known proteins. The first protein to be translated is the N-terminal protease (N). N helps evade the innate interferon response by targeting interferon regulatory factor-3 for proteasomal degradation and also participates in the evasion of dsRNA-induced apoptosis. To elucidate the mechanisms by which N functions, we performed a yeast two-hybrid screen in which the anti-apoptotic protein HAX-1 was identified. The N–HAX-1 interaction was confirmed using co-precipitation assays. A dramatic redistribution of both N and HAX-1 was observed in co-transfected cells, as well as in transfected cells infected with wild-type CSFV, but not in cells infected with an N-deleted CSFV strain.

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2010-11-01
2024-04-26
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References

  1. Al-Maghrebi, M., Brule, H., Padkina, M., Allen, C., Holmes, W. M. & Zehner, Z. E.(2002). The 3′ untranslated region of human vimentin mRNA interacts with protein complexes containing eEF-1γ and HAX-1. Nucleic Acids Res 30, 5017–5028.[CrossRef] [Google Scholar]
  2. Baigent, S. J., Zhang, G., Fray, M. D., Flick-Smith, H., Goodbourn, S. & McCauley, J. W.(2002). Inhibition of beta interferon transcription by noncytopathogenic bovine viral diarrhea virus is through an interferon regulatory factor 3-dependent mechanism. J Virol 76, 8979–8988.[CrossRef] [Google Scholar]
  3. Baigent, S. J., Goodbourn, S. & McCauley, J. W.(2004). Differential activation of interferon regulatory factors-3 and -7 by non-cytopathogenic and cytopathogenic bovine viral diarrhoea virus. Vet Immunol Immunopathol 100, 135–144.[CrossRef] [Google Scholar]
  4. Banerjee, A., Saito, K., Meyer, K., Banerjee, S., Ait-Goughoulte, M., Ray, R. B. & Ray, R.(2009). Hepatitis C virus core protein and cellular protein HAX-1 promotes 5-fluorouracil mediated hepatocyte growth inhibition. J Virol 83, 9663–9671.[CrossRef] [Google Scholar]
  5. Bauhofer, O., Summerfield, A., Sakoda, Y., Tratschin, J. D., Hofmann, M. A. & Ruggli, N.(2007). Classical swine fever virus Npro interacts with interferon regulatory factor 3 and induces its proteasomal degradation. J Virol 81, 3087–3096.[CrossRef] [Google Scholar]
  6. Bensaude, E., Turner, J. L. E., Wakeley, P. R., Sweetman, D. A., Pardieu, C., Drew, T. W., Wileman, T. & Powel, P. P.(2004). Classical swine fever virus induces proinflammatory cytokines and tissue factor expression and inhibits apoptosis and interferon synthesis during the establishment of long-term infection of porcine vascular endothelial cells. J Gen Virol 85, 1029–1037.[CrossRef] [Google Scholar]
  7. Carrillo, A., Chamorro, S., Rodríguez-Gago, M., Álvarez, B., Molina, M. J., Rodríguez-Barbosa, J. I., Sánchez, A., Ramírez, P., Muñoz, A. & other authors(2002). Isolation and characterisation of immortalised porcine aortic endothelial cell lines. Vet Immunol Immunopathol 89, 91–98.[CrossRef] [Google Scholar]
  8. Chao, J.-R., Parganas, E., Boyd, K., Hong, C. Y., Opferman, J. T. & Ihle, J. N.(2008). Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons. Nature 452, 98–102.[CrossRef] [Google Scholar]
  9. Charleston, B., Fray, M. D., Baigent, S., Carr, B. V. & Morrison, W. I.(2001). Establishment of persistent infection with non-cytopathic bovine viral diarrhoea virus in cattle is associated with a failure to induce type I interferon. J Gen Virol 82, 1893–1897. [Google Scholar]
  10. Chen, Z., Rijnbrand, R., Jangra, R. K., Devaraj, S. G., Qu, L., Ma, Y., Lemon, S. M. & Li, K.(2007). Ubiquitination and proteasomal degradation of interferon regulatory factor-3 induced by Npro from a cytopathic bovine viral diarrhea virus. Virology 366, 277−–292.[CrossRef] [Google Scholar]
  11. Cilenti, L., Soundarapandian, M. M., Kyriazis, G. A., Stratico, V., Singh, S., Gupta, S., Bonventre, J. V., Alnemri, E. S. & Zervos, A. S.(2004). Regulation of HAX-1 anti-apoptotic protein by Omi/HtrA2 protease during cell death. J Biol Chem 279, 50295–50301.[CrossRef] [Google Scholar]
  12. Doceul, V., Charleston, B., Crooke, H., Reid, E., Powell, P. P. & Seago, J.(2008). The Npro product of classical swine fever virus interacts with IκBα, the NF-κB inhibitor. J Gen Virol 89, 1881–1889.[CrossRef] [Google Scholar]
  13. Dufva, M., Olsson, M. & Rymo, L.(2001). Epstein–Barr virus nuclear antigen 5 interacts with HAX-1, a possible component of the B-cell receptor signalling pathway. J Gen Virol 82, 1581–1587. [Google Scholar]
  14. Fadeel, B. & Grzybowska, E.(2009). HAX-1: a multifunctional protein with emerging roles in human disease. Biochim Biophys Acta 1790, 1139–1148.[CrossRef] [Google Scholar]
  15. Forsman, A., Ruetschi, U., Ekholm, J. & Rymo, L.(2008). Identification of Intracellular proteins associated with the EBV-encoded nuclear antigen 5 using an efficient TAP procedure and FT-ICR mass spectrometry. J Proteome Res 7, 2309–2319.[CrossRef] [Google Scholar]
  16. Gallagher, A. R., Cedzich, A., Gretz, N., Somlo, S. & Witzgall, R.(2000). The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton. Proc Natl Acad Sci U S A 97, 4017–4022.[CrossRef] [Google Scholar]
  17. Hacki, J., Egger, L., Monney, L., Conus, S., Rosse, T., Fellay, I. & Borner, C.(2000). Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2. Oncogene 19, 2286–2295.[CrossRef] [Google Scholar]
  18. Han, Y., Chen, Y. S., Liu, Z., Bodyak, N., Rigor, D., Bisping, E., Pu, W. T. & Kang, P. M.(2006). Overexpression of HAX-1 protects cardiac myocytes from apoptosis through caspase-9 inhibition. Circ Res 99, 415–423.[CrossRef] [Google Scholar]
  19. Hilton, L., Moganeradj, K., Zhang, G., Chen, Y. H., Randall, R. E., McCauley, J. W. & Goodbourn, S.(2006). The Npro product of bovine viral diarrhea virus inhibits DNA binding by interferon regulatory factor 3 and targets it for proteasomal degradation. J Virol 80, 11723–11732.[CrossRef] [Google Scholar]
  20. Hippe, A., Bylaite, M., Chen, M., von Mikecz, A., Wolf, R., Ruzicka, T. & Walz, M.(2006). Expression and tissue distribution of mouse Hax1. Gene 379, 116–126.[CrossRef] [Google Scholar]
  21. Horscroft, N., Bellows, D., Ansari, I., Lai, V. C., Dempsey, S., Liang, D., Donis, R., Zhong, W. & Hong, Z.(2005). Establishment of a subgenomic replicon for bovine viral diarrhea virus in Huh-7 cells and modulation of interferon-regulated factor 3-mediated antiviral response. J Virol 79, 2788–2796.[CrossRef] [Google Scholar]
  22. Jeyaraju, D. V., Cisbani, G., De Brito, O. M., Koonin, E. V. & Pellegrini, L.(2009). Hax1 lacks BH modules and is peripherally associated to heavy membranes: implications for Omi/HtrA2 and PARL activity in the regulation of mitochondrial stress and apoptosis. Cell Death Differ 16, 1622–1629.[CrossRef] [Google Scholar]
  23. Johns, H. L., Bensaude, E., La Rocca, S. A., Seago, J., Charleston, B., Steinbach, F., Drew, T. W., Crooke, H. & Everett, H.(2010). Classical swine fever virus infection protects aortic endothelial cells from pIpC-mediated apoptosis. J Gen Virol 91, 1038−–1046.[CrossRef] [Google Scholar]
  24. Kawaguchi, Y., Nakajima, K., Igarashi, M., Morita, T., Tanaka, M., Suzuki, M., Yokoyama, A., Matsuda, G., Kato, K. & other authors(2000). Interaction of Epstein–Barr virus nuclear antigen leader protein (EBNA-LP) with HS1-associated protein X-1: implication of cytoplasmic function of EBNA-LP. J Virol 74, 10104–10111.[CrossRef] [Google Scholar]
  25. Kawaguchi, Y., Nishimagi, E., Tochimoto, A., Kawamoto, M., Katsumata, Y., Soejima, M., Kanno, T., Kamatani, N. & Hara, M.(2006). Intracellular IL-1α-binding proteins contribute to biological functions of endogenous IL-1α in systemic sclerosis fibroblasts. Proc Natl Acad Sci U S A 103, 14501–14506.[CrossRef] [Google Scholar]
  26. La Rocca, S. A., Herbert, R. J., Crooke, H., Drew, T. W., Wileman, T. E. & Powell, P. P.(2005). Loss of interferon regulatory factor 3 in cells infected with classical swine fever virus involves the N-terminal protease, Npro. J Virol 79, 7239–7247.[CrossRef] [Google Scholar]
  27. Lee, A. Y., Lee, Y., Park, Y. K., Bae, K. H., Cho, S., Lee do, H., Park, B. C., Kang, S. & Park, S. G.(2008). HS 1-associated protein X-1 is cleaved by caspase-3 during apoptosis. Mol Cells 25, 86–90. [Google Scholar]
  28. Lees, D. M., Hart, I. R. & Marshall, J. F.(2008). Existence of multiple isoforms of HS1-associated protein X-1 in murine and human tissues. J Mol Biol 379, 645–655.[CrossRef] [Google Scholar]
  29. Le Potier, M., Mesplede, A. & Vannier, P.(2006). Classical swine fever and other pestiviruses. In Diseases of Swine, 9th edn, pp. 309–322. Edited by Straw, B. E., Zimmerman, J. J., D'Allaire, S. & Taylor, D. J.. Ames, IA. : Blackwell. [Google Scholar]
  30. Lindenbach, B. D., Thiel, H. J. & Rice, C. M.(2007).Flaviviridae: the viruses and their replication. In Fields Virology, 5th edn, pp. 1101–1152. Edited by Knipe, D. M. & Howley, P. M.. Philadelphia, PA. : LW&W. [Google Scholar]
  31. Matsuda, G., Nakajima, K., Kawaguchi, Y., Yamanashi, Y. & Hirai, K.(2003). Epstein–Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) forms complexes with a cellular anti-apoptosis protein Bcl-2 or its EBV counterpart BHRF1 through HS1-associated protein X-1. Microbiol Immunol 47, 91–99.[CrossRef] [Google Scholar]
  32. Modem, S. & Reddy, R. T.(2008). An anti-apoptotic protein, Hax-1, inhibits the HIV-1 rev function by altering its sub-cellular localization. J Cell Physiol 214, 14–19.[CrossRef] [Google Scholar]
  33. Nettleton, P. F., Gilray, J. A., Russo, P. & Dlissi, E.(1998). Border disease of sheep and goats. Vet Res 29, 327–340. [Google Scholar]
  34. Peterhans, E. & Schweizer, M.(2010). Pestiviruses: how to outmaneuver your hosts. Vet Microbiol 142, 18–25.[CrossRef] [Google Scholar]
  35. Ribbens, S., Dewulf, J., Koenen, F., Laevens, H. & Kruif, A.(2004). Transmission of classical swine fever. A review. Vet Q 26, 146–155.[CrossRef] [Google Scholar]
  36. Rouiller, I., Brookes, S. M., Hyatt, A. D., Windsor, M. & Wileman, T.(1998). African swine fever virus is wrapped by the endoplasmic reticulum. J Virol 72, 2373–2387. [Google Scholar]
  37. Rudner, J., Lepple-Wienhues, A., Budach, W., Berschauer, J., Friedrich, B., Wesselborg, S., Schulze-Osthoff, K. & Belka, C.(2001). Wild-type, mitochondrial and ER-restricted Bcl-2 inhibit DNA damage-induced apoptosis but do not affect death receptor-induced apoptosis. J Cell Sci 114, 4161–4172. [Google Scholar]
  38. Ruggli, N., Tratschin, J. D., Schweizer, M., McCullough, K. C., Hofmann, M. A. & Summerfield, A.(2003). Classical swine fever virus interferes with cellular antiviral defense: evidence for a novel function of Npro. J Virol 77, 7645–7654.[CrossRef] [Google Scholar]
  39. Ruggli, N., Bird, B. H., Liu, L., Bauhofer, O., Tratschin, J. D. & Hofmann, M. A.(2005). Npro of classical swine fever virus is an antagonist of double-stranded RNA-mediated apoptosis and IFN-α/β induction. Virology 340, 265–276.[CrossRef] [Google Scholar]
  40. Schweizer, M. & Peterhans, E.(2001). Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced apoptosis and interferon synthesis. J Virol 75, 4692–4698.[CrossRef] [Google Scholar]
  41. Seago, J., Hilton, L., Reid, E., Doceul, V., Jeyatheesan, J., Moganeradj, K., McCauley, J., Charleston, B. & Goodbourn, S.(2007). The Npro product of classical swine fever virus and bovine viral diarrhea virus uses a conserved mechanism to target interferon regulatory factor-3. J Gen Virol 88, 3002–3006.[CrossRef] [Google Scholar]
  42. Sharp, T. V., Wang, H. W., Koumi, A., Hollyman, D., Endo, Y., Ye, H., Du, M. Q. & Boshoff, C.(2002). K15 protein of Kaposi's sarcoma-associated herpesvirus is latently expressed and binds to HAX-1, a protein with antiapoptotic function. J Virol 76, 802–816.[CrossRef] [Google Scholar]
  43. Shaw, J. & Kirshenbaum, L. A.(2006). HAX-1 represses postmitochondrial caspase-9 activation and cell death during hypoxia–reoxygenation. Circ Res 99, 336–338.[CrossRef] [Google Scholar]
  44. Suzuki, Y., Demoliere, C., Kitamura, D., Takeshita, H., Deuschle, U. & Watanabe, T.(1997). HAX-1, a novel intracellular protein, localized on mitochondria, directly associates with HS1, a substrate of Src family tyrosine kinases. J Immunol 158, 2736–2744. [Google Scholar]
  45. Vafiadaki, E., Sanoudou, D., Arvanitis, D. A., Catino, D. H., Kranias, E. G. & Kontrogianni-Konstantopoulos, A.(2007). Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function. J Mol Biol 367, 65–79.[CrossRef] [Google Scholar]
  46. Yedavalli, V. S., Shih, H. M., Chiang, Y. P., Lu, C. Y., Chang, L. Y., Chen, M. Y., Chuang, C. Y., Dayton, A. I., Jeang, K. T. & Huang, L. M.(2005). Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1. J Virol 79, 13735–13746.[CrossRef] [Google Scholar]
  47. Yin, H., Morioka, H., Towle, C. A., Vidal, M., Watanabe, T. & Weissbach, L.(2001). Evidence that HAX-1 is an interleukin-1α N-terminal binding protein. Cytokine 15, 122–137.[CrossRef] [Google Scholar]
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The classical swine fever virus N-terminal protease Npro binds to cellular HAX-1
J. Gen. Virol. 91, 2677 (2010); https://doi.org/10.1099/vir.0.022897-0
/content/journal/jgv/10.1099/vir.0.022897-0
/content/journal/jgv/10.1099/vir.0.022897-0
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