ACBD3-mediated Recruitment of PI4KB to Picornavirus RNA Replication Sites

EMBO J. 2012 Feb 1;31(3):754-66. doi: 10.1038/emboj.2011.429. Epub 2011 Nov 29.

Abstract

Phosphatidylinositol 4-kinase IIIβ (PI4KB) is a host factor required for genome RNA replication of enteroviruses, small non-enveloped viruses belonging to the family Picornaviridae. Here, we demonstrated that PI4KB is also essential for genome replication of another picornavirus, Aichi virus (AiV), but is recruited to the genome replication sites by a different strategy from that utilized by enteroviruses. AiV non-structural proteins, 2B, 2BC, 2C, 3A, and 3AB, interacted with a Golgi protein, acyl-coenzyme A binding domain containing 3 (ACBD3). Furthermore, we identified previously unknown interaction between ACBD3 and PI4KB, which provides a novel manner of Golgi recruitment of PI4KB. Knockdown of ACBD3 or PI4KB suppressed AiV RNA replication. The viral proteins, ACBD3, PI4KB, and phophatidylinositol-4-phosphate (PI4P) localized to the viral RNA replication sites. AiV replication and recruitment of PI4KB to the RNA replication sites were not affected by brefeldin A, in contrast to those in enterovirus infection. These results indicate that a viral protein/ACBD3/PI4KB complex is formed to synthesize PI4P at the AiV RNA replication sites and plays an essential role in viral RNA replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • DNA Primers
  • Electroporation
  • Gene Silencing
  • Humans
  • Membrane Proteins / physiology*
  • Microscopy, Fluorescence
  • Minor Histocompatibility Antigens
  • Molecular Sequence Data
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Picornaviridae / physiology*
  • Virus Replication*

Substances

  • ACBD3 protein, human
  • Adaptor Proteins, Signal Transducing
  • DNA Primers
  • Membrane Proteins
  • Minor Histocompatibility Antigens
  • Phosphotransferases (Alcohol Group Acceptor)
  • phosphatidylinositol phosphate 4-kinase