Inhibition of cellular protein secretion by norwalk virus nonstructural protein p22 requires a mimic of an endoplasmic reticulum export signal.
Protein trafficking between the endoplasmic reticulum (ER) and Golgi apparatus is central to cellular homeostasis. ER export signals are utilized by a subset of proteins to rapidly exit the ER by direct uptake into COPII vesicles for transport to the Golgi. Norwalk virus nonstructural protein p22 contains a YXΦESDG motif that mimics a di-acidic ER export signal in both sequence and function. However, unlike normal ER export signals, the ER export signal mimic of p22 is necessary for apparent inhibition of normal COPII vesicle trafficking, which leads to Golgi disassembly and antagonism of Golgi-dependent cellular protein secretion. This is the first reported function for p22. Disassembly of the Golgi apparatus was also observed in cells replicating Norwalk virus, which may contribute to pathogenesis by interfering with cellular processes that are dependent on an intact secretory pathway. These results indicate that the ER export signal mimic is critical to the antagonistic function of p22, shown herein to be a novel antagonist of ER/Golgi trafficking. This unique and well-conserved human norovirus motif is therefore an appealing target for antiviral drug development.
Sharp
Tyler M
TM
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
Guix
Susana
S
Katayama
Kazuhiko
K
Crawford
Sue E
SE
Estes
Mary K
MK
D000595:Amino Acid Sequence; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D008854:Microscopy, Electron; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009663:Norwalk virus / Q000502:physiology*; D049790:Nuclear Export Signals; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D014779:Virus Replication
D049790:Nuclear Export Signals; D017361:Viral Nonstructural Proteins