Rhabdoviruses and the cellular ubiquitin-proteasome system

A budding interaction

R. N. Harty, M. E. Brown, J. P. McGettigan, G. Wang, H. R. Jayakar, J. M. Huibregtse, Michael Whitt, M. J. Schnell

Research output: Contribution to journalArticle

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Abstract

The matrix (M) proteins of vesicular stomatitis virus (VSV) and rabies virus (RV) play a key role in both assembly and budding of progeny virions. A PPPY motif (PY motif or late-budding domain) is conserved in the M proteins of VSV and RV. These PY motifs are important for virus budding and for mediating interactions with specific cellular proteins containing WW domains. The PY motif and flanking sequences of the M protein of VSV were used as bait to screen a mouse embryo cDNA library for cellular interactors. The mouse Nedd4 protein, a membrane-localized ubiquitin ligase containing multiple WW domains, was identified from this screen. Ubiquitin ligase Rsp5, the yeast homolog of Nedd4, was able to interact both physically and functionally with full-length VSV M protein in a PY-dependent manner. Indeed, the VSV M protein was multiubiquitinated by Rsp5 in an in vitro ubiquitination assay. To demonstrate further that ubiquitin may be involved in the budding process of rhabdoviruses, proteasome inhibitors (e.g., MG132) were used to decrease the level of free ubiquitin in VSV- and RV-infected cells. Viral titers measured from MG132-treated cells were reproducibly 10- to 20-fold lower than those measured from untreated control cells, suggesting that free ubiquitin is important for efficient virus budding. Last, release of a VSV PY mutant was not inhibited in the presence of MG132, signifying that the functional L domain of VSV is required for the inhibitory effect exhibited by MG132. These data suggest that the cellular ubiquitin-proteasome machinery is involved in the budding process of VSV and RV.

Original languageEnglish (US)
Pages (from-to)10623-10629
Number of pages7
JournalJournal of Virology
Volume75
Issue number22
DOIs
StatePublished - Nov 15 2001

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Rhabdoviridae
Vesiculovirus
proteasome endopeptidase complex
Proteasome Endopeptidase Complex
ubiquitin
Ubiquitin
Rabies virus
Vesicular Stomatitis
Viruses
Virus Release
Ligases
proteins
ligases
Proteasome Inhibitors
Ubiquitination
Gene Library
Virion
viruses
Embryonic Structures
Yeasts

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Harty, R. N., Brown, M. E., McGettigan, J. P., Wang, G., Jayakar, H. R., Huibregtse, J. M., ... Schnell, M. J. (2001). Rhabdoviruses and the cellular ubiquitin-proteasome system: A budding interaction. Journal of Virology, 75(22), 10623-10629. https://doi.org/10.1128/JVI.75.22.10623-10629.2001

Rhabdoviruses and the cellular ubiquitin-proteasome system : A budding interaction. / Harty, R. N.; Brown, M. E.; McGettigan, J. P.; Wang, G.; Jayakar, H. R.; Huibregtse, J. M.; Whitt, Michael; Schnell, M. J.

In: Journal of Virology, Vol. 75, No. 22, 15.11.2001, p. 10623-10629.

Research output: Contribution to journalArticle

Harty, RN, Brown, ME, McGettigan, JP, Wang, G, Jayakar, HR, Huibregtse, JM, Whitt, M & Schnell, MJ 2001, 'Rhabdoviruses and the cellular ubiquitin-proteasome system: A budding interaction', Journal of Virology, vol. 75, no. 22, pp. 10623-10629. https://doi.org/10.1128/JVI.75.22.10623-10629.2001
Harty RN, Brown ME, McGettigan JP, Wang G, Jayakar HR, Huibregtse JM et al. Rhabdoviruses and the cellular ubiquitin-proteasome system: A budding interaction. Journal of Virology. 2001 Nov 15;75(22):10623-10629. https://doi.org/10.1128/JVI.75.22.10623-10629.2001
Harty, R. N. ; Brown, M. E. ; McGettigan, J. P. ; Wang, G. ; Jayakar, H. R. ; Huibregtse, J. M. ; Whitt, Michael ; Schnell, M. J. / Rhabdoviruses and the cellular ubiquitin-proteasome system : A budding interaction. In: Journal of Virology. 2001 ; Vol. 75, No. 22. pp. 10623-10629.
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