An unrecognized function for COPII components in recruiting a viral replication protein to the perinuclear ER

Abstract

Positive-strand RNA viruses invariably assemble their viral replication complexes (VRCs) by remodeling host intracellular membranes. How viral replication proteins are targeted to specific organelle membranes to initiate VRC assembly remains elusive. Brome mosaic virus (BMV), whose replication can be recapitulated in Saccharomyces cerevisiae, assembles its VRCs by invaginating the outer perinuclear ER membrane. Remarkably, BMV replication protein 1a (BMV 1a) is the only viral protein required for such membrane remodeling. We show that Erv14 (ER-vesicle protein of 14 kD), a cargo receptor of coat protein complex II (COPII), interacts with BMV 1a. Moreover, BMV 1a's perinuclear ER localization is disrupted in cells lacking ERV14 or expressing dysfunctional COPII coats (Sec13, Sec24, or Sec31). The requirement of Erv14 for BMV 1a's localization is bypassed by addition of a Sec24-recognizable sorting signal to BMV 1a or by overexpressing Sec24, suggesting a coordinated effort by both Erv14 and Sec24 for BMV 1a's proper localization. The COPII pathway is well known for protein secretion; our data suggest an unrecognized role by a subset of COPII coats in targeting proteins to the perinuclear ER membrane.