Ubiquitin depletion and dominant-negative VPS4 inhibit rhabdovirus budding without affecting alphavirus budding

Gwen M. Taylor, Phyllis I. Hanson, Margaret Kielian

Research output: Contribution to journalArticle

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Abstract

The budding reactions of a number of enveloped viruses use the cellular machinery involved in the formation of the luminal vesicles of endosomal multivesicular bodies (MVB). Budding of these viruses is dependent on the presence of specific late-domain motifs in membrane-associated viral proteins. Such budding reactions usually involve ubiquitin and are blocked by expression of an ATPase-deficient form of VPS4, a cellular AAA+ ATPase believed to be required late in the MVB pathway for the disassembly/release of the MVB machinery. Here we examined the role of the MVB pathway in the budding of the late-domain-containing rhabdovirus vesicular stomatitis virus (VSV) and the alphavirus Semliki Forest virus (SFV). We tested early and late steps in the MVB pathway by depleting ubiquitin with the proteasome inhibitor MG-132 and by using cell lines inducibly expressing VPS4A or VPS4B protein. As previously shown, VSV budding was strongly dependent on ubiquitin. In contrast to the findings of previous studies with VPS4A, expression of ATPase-deficient mutants of either VPS4A or VPS4B inhibited VSV budding. Inhibition by VPS4 required the presence of the PPPY late domain on the VSV matrix protein and resulted in the accumulation of nonreleased VSV particles at the plasma membrane. In contrast, SFV budding was independent of both ubiquitin and the activity of VPS4, perhaps reflecting the important role of the highly organized envelope protein lattice during alphavirus budding.

Original languageEnglish (US)
Pages (from-to)13631-13639
Number of pages9
JournalJournal of Virology
Volume81
Issue number24
DOIs
StatePublished - Dec 2007

Fingerprint

Rhabdoviridae
Alphavirus
Multivesicular Bodies
Vesiculovirus
Vesicular Stomatitis
Virus Release
ubiquitin
Ubiquitin
Semliki Forest virus
Semliki forest virus
adenosinetriphosphatase
Adenosine Triphosphatases
Viruses
viruses
Proteins
Proteasome Inhibitors
proteins
viral proteins
proteasome endopeptidase complex
virion

ASJC Scopus subject areas

  • Immunology

Cite this

Ubiquitin depletion and dominant-negative VPS4 inhibit rhabdovirus budding without affecting alphavirus budding. / Taylor, Gwen M.; Hanson, Phyllis I.; Kielian, Margaret.

In: Journal of Virology, Vol. 81, No. 24, 12.2007, p. 13631-13639.

Research output: Contribution to journalArticle

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