1887

Journal of General Virology header logo

Volume 84, Issue 12

Transfection of prion protein gene suppresses coxsackievirus B3 replication in prion protein gene-deficient cells Free

Abstract

The susceptibility of prion protein gene ()-null cells to coxsackievirus B3 (CVB3) was investigated. Primary cultures of murine brain cells were more sensitive to CVBs than corresponding cells from wild-type mice. The viral susceptibility of a -null cell line (HpL3-4) derived from the murine hippocampus was compared with that of two established cell lines (HeLa and HEp-2) that are widely employed for CVB3 studies. After infection with CVB3, HpL3-4 cells showed a very rapid and complete cytopathic effect (CPE). CPE developed earlier and viruses replicated at higher titres in HpL3-4 cells compared with HeLa and HEp-2 cells. Under a semi-solid medium, plaques developed rapidly in CVB3-infected HpL3-4 cells. To confirm the effect of on virus infection, a cell line and a -transfected neuronal cell line were analysed. The replication and release of infectious particles of CVB3 in cells were significantly more effective than those of the -transfected cell line. Levels of type I interferon (IFN) after CVB3 infection were higher in the -transfected cell line than in cells, whereas apoptotic cells were more obvious in the cells than in those of the -transfected cell line. These findings suggest that the absence of retards the induction of CVB3-induced IFNs, resulting in an enhanced CVB3 production and apoptotic cell death. Furthermore, our data indicate that the HpL3-4 cell line may provide a novel and sensitive system for isolation of CVB3 from clinical specimens.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19222-0
2003-12-01
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/12/vir843495.html?itemId=/content/journal/jgv/10.1099/vir.0.19222-0&mimeType=html&fmt=ahah

References

  1. Akowitz A., Sklaviadis T., Manuelidis L. 1994; Endogenous viral complexes with long RNA cosediment with the agent of Creutzfeldt–Jakob disease. Nucleic Acids Res 22:1101–1107
     [Google Scholar]
  2. Blom W. M., De Bont H. J., Nagelkelke J. F. 2003; Regional loss of the mitochondrial membrane potential in the hepatocytes is rapidly followed by externalization of phosphatidyl serines at that specific site during apoptosis. J Biol Chem 278:12467–12474
     [Google Scholar]
  3. Bounhar Y., Zhang Y., Goodyer C. G., LeBlanc A. 2001; Prion protein protects human neurons against Bax-mediated apoptosis. J Biol Chem 276:145–149
     [Google Scholar]
  4. Carp R., Meeker H., Caruso V., Sersen E. 1999; Scrapie strain-specific interactions with endogenous murine leukaemia virus. J Gen Virol 80:5–10
     [Google Scholar]
  5. Carthy C. M., Granville D. J., Easton K. A., Anderson D. R., Wilson J. E., Yang D., Hunt D. W., McManus B. M. 1998; Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in Hela cells. J Virol 73:7669–7675
     [Google Scholar]
  6. Caughey B., Brown K., Raymond G., Katzenstein G., Thresher W. 1994; Binding of the protease-sensitive form of PrP (prion protein) to sulfated glycosaminoglycan and congo red. J Virol 68:2135–2141
     [Google Scholar]
  7. Colston J. T., Chandrasekar B., Freeman G. L. 1998; Expression of apoptosis-related proteins in experimental coxsackievirus myocarditis. Cardiovascular Res 38:158–168
     [Google Scholar]
  8. Darlix J.-L., Lapadat-Tapolsky M., de Rocquigny H., Roques B. 1995; First glimpses at structure–function relationships of the nucleocapsid protein of retroviruses. J Mol Biol 254:523–537
     [Google Scholar]
  9. DeArmond S. J., Mobley W. C., DeMott D. L., Barry R. A., Beckstead J. H., Prusiner S. B. 1987; Changes in the localization of brain prion proteins during scrapie infection. Neurology 37:1271–1280
     [Google Scholar]
  10. Gabus C., Derrington E., Leblanc P. 8 other authors 2001; The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-1. J Biol Chem 276:19301–19309
     [Google Scholar]
  11. Harris D. A., Lele P., Snider W. D. 1993; Localization of the mRNA for a chicken prion protein by in situ hybridization. Proc Natl Acad Sci U S A 90:4309–4313
     [Google Scholar]
  12. Kretzschmar H., Prusiner S. B., Stowring L., DeArmond S. 1986; Scrapie prion proteins are synthesized in neurons. Am J Pathol 122:1–5
     [Google Scholar]
  13. Kuwahara C., Takeuchi A. M., Nishimura T. 8 other authors 1999; Prions prevent neuronal cell-line death. Nature 400:225–226
     [Google Scholar]
  14. Manson J., West J. D., Thomson V., McBride P., Kaufman M. H., Hope J. 1992; The prion protein gene: a role in mouse embryogenesis?. Development 115:117–122
     [Google Scholar]
  15. Nandi P. K., Leclerc E. 1999; Polymerization of murine recombinant prion protein in nucleic acid solution. Arch Virol 144:1751–1763
     [Google Scholar]
  16. Prusiner S. B., Scott M., DeArmond S., Cohen F. 1998; Prion protein biology. Cell 93:337–348
     [Google Scholar]
  17. Rotbart H. A. 1995; Enteroviral infections of the central nervous system. Clin Infect Dis 20:971–981
     [Google Scholar]
  18. Schatzl H. M., Laszlo L., Holtman D. N., Tatzelt J., Dermond S. J., Weiner R. I., Mobley W. C., Prusiner S. B. 1997; A hypothalamic neural cell line persistently infected with scrapie prions exhibits apoptosis. J Virol 71:8821–8831
     [Google Scholar]
  19. Selinka H.-C., Huber M., Pasch A., Klingel K., Aepinus C., Kandolf R. 1998; Coxsackie B virus and its interaction with permissive host cells. Clin Diagn Virol 9:115–112
     [Google Scholar]
  20. Ward L. A., Massa P. T. 1995; Neuron-specific regulation of major histocompatibility complex class I, interferon-beta, and anti-viral state genes. J Neuroimmunol 58:145–155
     [Google Scholar]
  21. Weiss S., Neumann M., Groschup M., Kretzschmar H., Famulok M., Winnacker E. 1997; RNA aptamers specifically interact with the prion protein PrP. J Virol 71:8790–8797
     [Google Scholar]
  22. Woodruff J. F. 1980; Viral myocarditis: a review. Am J Pathol 101:425–483
     [Google Scholar]
  23. Xu R., Crowell R. L. 1996; Expression and distribution of the receptors for coxsackievirus B3 during fetal development of the Balb/c mouse and of their brain cells in culture. Virus Res 46:157–170
     [Google Scholar]
  24. Yang C. H., Murti A., Pfetter S. R., Kim J. G., Donner D. B., Ptetter L. M. 2001; Interferon α / β promote cell survival by activating nuclear factor κ B through phosphatidylinositol 3-kinase and Akt. J Biol Chem 276:13756–13761
     [Google Scholar]
  25. Zanusso G., Liu D., Ferrari S. 11 other authors 1998; Prion protein expression in different species: analysis with a panel of new mAbs. Proc Natl Acad Sci U S A 95:8812–8816
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19222-0
Loading
Transfection of prion protein gene suppresses coxsackievirus B3 replication in prion protein gene-deficient cells
J. Gen. Virol. 84, 3495 (2003); https://doi.org/10.1099/vir.0.19222-0
/content/journal/jgv/10.1099/vir.0.19222-0
/content/journal/jgv/10.1099/vir.0.19222-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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