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RNAi screening reveals proteasome- and Cullin3-dependent stages in vaccinia virus infection.
Journal article

RNAi screening reveals proteasome- and Cullin3-dependent stages in vaccinia virus infection.

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  • 2012-10-23
Published in:
  • Cell reports. - 2012
Computational Biology
Cullin Proteins
DNA Replication
DNA, Viral
HeLa Cells
Humans
Proteasome Endopeptidase Complex
RNA Interference
RNA, Small Interfering
Ubiquitination
Vaccinia
Vaccinia virus
English A two-step, automated, high-throughput RNAi silencing screen was used to identify host cell factors required during vaccinia virus infection. Validation and analysis of clustered hits revealed previously unknown processes during virus entry, including a mechanism for genome uncoating. Viral core proteins were found to be already ubiquitinated during virus assembly. After entering the cytosol of an uninfected cell, the viral DNA was released from the core through the activity of the cell's proteasomes. Next, a Cullin3-based ubiquitin ligase mediated a further round of ubiquitination and proteasome action. This was needed in order to initiate viral DNA replication. The results accentuate the value of large-scale RNAi screens in providing directions for detailed cell biological investigation of complex pathways. The list of cell functions required during poxvirus infection will, moreover, provide a resource for future virus-host cell interaction studies and for the discovery of antivirals.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/126894
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