siRNA screen of early poxvirus genes identifies the AAA+ ATPase D5 as the virus genome-uncoating factor

Samuel Kilcher, Florian Ingo Schmidt, Christoph Schneider, Manfred Kopf, Ari Helenius, Jason Mercer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)
212 Downloads (Pure)

Abstract

Summary Poxvirus genome uncoating is a two-step process. First, cytoplasmic viral cores are activated and early viral genes are expressed. Next, cores are disassembled and the genomes released. This second step depends on an early viral factor(s) that has eluded identification for over 40 years. We used a large-scale, high-throughput RNAi screen directed against vaccinia virus (VACV) to identify the VACV AAA+ ATPase D5 as the poxvirus uncoating factor. We show that the ATPase activity of D5 is required for uncoating. Superresolution microscopy suggests that D5 acts directly at viral cores for genome release. Thus, the putative helicase D5 is a multifunctional protein required for genome uncoating and replication. Additionally, in vivo delivery of anti-D5 siRNAs reduced virus production in a mouse model of VACV infection. These results demonstrate the use of virus-targeting RNAi libraries to investigate viral gene function and suggest therapeutic avenues.

Original languageEnglish
Pages (from-to)103-112
Number of pages10
JournalCell Host and Microbe
Volume15
Issue number1
DOIs
Publication statusPublished - 15 Jan 2014

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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