1887

Abstract

(VSV) is a rhabdovirus that has attracted attention of late as an oncolytic virus and as a vaccine vector. Mutations in the matrix (M) gene of VSV yield attenuated strains that may be very useful in both settings. As a result of this interest in the M protein, this study analysed various M–green fluorescent protein (GFP) fusion constructs. Remarkably, fusion of the N terminus of the M protein to GFP targeted the fluorescent protein to the surface of mitochondria. Mutational analysis indicated that a mitochondrial-targeting motif exists within aa 33–67. Expression of these fusion proteins led to loss of mitochondrial membrane permeability and to an alteration in mitochondrial organization mirroring that seen during viral infection. In addition, a portion of the M protein present in infected cells co-purified with mitochondria. This work may indicate a novel function for this multifunctional viral protein.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81762-0
2006-11-01
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/11/3379.html?itemId=/content/journal/jgv/10.1099/vir.0.81762-0&mimeType=html&fmt=ahah

References

  1. Black B. L., Lyles D. S. 1992; Vesicular stomatitis virus matrix protein inhibits host cell-directed transcription of target genes in vivo. J Virol 66:4058–4064
    [Google Scholar]
  2. Blondel D., Harmison G. G., Schubert M. 1990; Role of matrix protein in cytopathogenesis of vesicular stomatitis virus. J Virol 64:1716–1725
    [Google Scholar]
  3. Boya P., Pauleau A.-L., Poncet D., Gonzalez-Polo R.-A., Zamzami N., Kroemer G. 2004; Viral proteins targeting mitochondria: controlling cell death. Biochim Biophys Acta 1659178–189 [CrossRef]
    [Google Scholar]
  4. Carroll A. R., Wagner R. R. 1979; Role of the membrane (M) protein in endogenous inhibition of in vitro transcription by vesicular stomatitis virus. J Virol 29:134–142
    [Google Scholar]
  5. Cavadini P., Gakh O., Isaya G. 2002; Protein import and processing reconstituted with isolated rat liver mitochondria and recombinant mitochondrial processing peptidase. Methods 26:298–306 [CrossRef]
    [Google Scholar]
  6. Clinton G. M., Little S. P., Hagen F. S., Huang A. S. 1978; The matrix (M) protein of vesicular stomatitis virus regulates transcription. Cell 15:1455–1462 [CrossRef]
    [Google Scholar]
  7. Everett H., Barry M., Lee S. F., Sun X., Graham K., Stone J., Bleackley R. C., McFadden G. 2000; M11L: a novel mitochondria-localized protein of myxoma virus that blocks apoptosis of infected leukocytes. J Exp Med 191:1487–1498 [CrossRef]
    [Google Scholar]
  8. Faria P. A., Chakraborty P., Levay A., Barber G. N., Ezelle H. J., Enninga J., Arana C., van Deursen J., Fontoura B. M. A. 2005; VSV disrupts the Rae1/mrnp41 mRNA nuclear export pathway. Mol Cell 17:93–102 [CrossRef]
    [Google Scholar]
  9. Gaddy D. F., Lyles D. S. 2005; Vesicular stomatitis viruses expressing wild-type or mutant M proteins activate apoptosis through distinct pathways. J Virol 79:4170–4179 [CrossRef]
    [Google Scholar]
  10. Gaudier M., Gaudin Y., Knossow M. 2002; Crystal structure of vesicular stomatitis virus matrix protein. EMBO J 21:2886–2892 [CrossRef]
    [Google Scholar]
  11. Glodowski D. R., Petersen J. M., Dahlberg J. E. 2002; Complex nuclear localization signals in the matrix protein of vesicular stomatitis virus. J Biol Chem 277:46864–46870 [CrossRef]
    [Google Scholar]
  12. Gordon D. M., Dancis A., Pain D. 2000; Mechanisms of mitochondrial protein import. Essays Biochem 36:61–73
    [Google Scholar]
  13. Harder Z., Zunino R., McBride H. 2004; Sumo1 conjugates mitochondrial substrates and participates in mitochondrial fission. Curr Biol 14:340–345 [CrossRef]
    [Google Scholar]
  14. Harty R. N., Brown M. E., McGettigan J. P., Wang G., Jayakar H. R., Huibregtse J. M., Whitt M. A., Schnell M. J. 2001; Rhabdoviruses and the cellular ubiquitin-proteasome system: a budding interaction. J Virol 75:10623–10629 [CrossRef]
    [Google Scholar]
  15. Itoh M., Hotta H., Homma M. 1998; Increased induction of apoptosis by a Sendai virus mutant is associated with attenuation of mouse pathogenicity. J Virol 72:2927–2934
    [Google Scholar]
  16. Jacotot E., Ravagnan L., Loeffler M. & 15 other authors 2000; The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore. J Exp Med 191:33–46 [CrossRef]
    [Google Scholar]
  17. Jayakar H. R., Murti K. G., Whitt M. A. 2000; Mutations in the PPPY motif of vesicular stomatitis virus matrix protein reduce virus budding by inhibiting a late step in virion release. J Virol 74:9818–9827 [CrossRef]
    [Google Scholar]
  18. Kopecky S. A., Lyles D. S. 2003a; The cell-rounding activity of the vesicular stomatitis virus matrix protein is due to the induction of cell death. J Virol 77:5524–5528 [CrossRef]
    [Google Scholar]
  19. Kopecky S. A., Lyles D. S. 2003b; Contrasting effects of matrix protein on apoptosis in HeLa and BHK cells infected with vesicular stomatitis virus are due to inhibition of host gene expression. J Virol 77:4658–4669 [CrossRef]
    [Google Scholar]
  20. Kopecky S. A., Willingham M. C., Lyles D. S. 2001; Matrix protein and another viral component contribute to induction of apoptosis in cells infected with vesicular stomatitis virus. J Virol 75:12169–12181 [CrossRef]
    [Google Scholar]
  21. McCormick A. L., Smith V. L., Chow D., Mocarski E. S. 2003; Disruption of mitochondrial networks by the human cytomegalovirus UL37 gene product viral mitochondrion-localized inhibitor of apoptosis. J Virol 77:631–641 [CrossRef]
    [Google Scholar]
  22. Mossman K., Lee S. F., Barry M., Boshkov L., McFadden G. 1996; Disruption of M-T5, a novel myxoma virus gene member of poxvirus host range superfamily, results in dramatic attenuation of myxomatosis in infected European rabbits. J Virol 70:4394–4410
    [Google Scholar]
  23. Park M.-S., García-Sastre A., Cros J. F., Basler C. F., Palese P. 2003; Newcastle disease virus V protein is a determinant of host range restriction. J Virol 77:9522–9532 [CrossRef]
    [Google Scholar]
  24. Petersen J. M., Her L.-S., Varvel V., Lund E., Dahlberg J. E. 2000; The matrix protein of vesicular stomatitis virus inhibits nucleocytoplasmic transport when it is in the nucleus and associated with nuclear pore complexes. Mol Cell Biol 20:8590–8601 [CrossRef]
    [Google Scholar]
  25. Petersen J. M., Her L.-S., Dahlberg J. E. 2001; Multiple vesiculoviral matrix proteins inhibit both nuclear export and import. Proc Natl Acad Sci U S A 98:8590–8595 [CrossRef]
    [Google Scholar]
  26. Stojdl D. F., Lichty B. D., tenOever B. R. & 12 other authors 2003; VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell 4:263–275 [CrossRef]
    [Google Scholar]
  27. von Kobbe C., van Deursen J. M. A., Rodrigues J. P., Sitterlin D., Bachi A., Wu X., Wilm M., Carmo-Fonseca M., Izaurralde E. 2000; Vesicular stomatitis virus matrix protein inhibits host cell gene expression by targeting the nucleoporin Nup98. Mol Cell 6:1243–1252 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81762-0
Loading
/content/journal/jgv/10.1099/vir.0.81762-0
Loading

Data & Media loading...

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