Abstract：
: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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Mercer J,Snijder B,Sacher R,Burkard C,Bleck CK,Stahlberg H,Pelkmans L,Helenius Adoi
10.1016/j.celrep.2012.09.003subject
Has Abstractpub_date
2012-10-25 00:00:00pages
1036-47issue
4issn
2211-1247pii
S2211-1247(12)00284-7journal_volume
2pub_type
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