title: Inhibition of cellular protein secretion by picornaviral 3A proteins.
abstract: During poliovirus infection, anterograde traffic between the endoplasmic reticulum and the Golgi is inhibited due to the action of 3A, an 87 amino acid viral protein. The ability of poliovirus protein 3A to inhibit ER-to-Golgi traffic is not required for virus growth. Instead, we have suggested that the inhibition of host protein secretion, shown to reduce the secretion of interferon-beta, IL-6, and IL-8 and the expression of both newly synthesized MHC class I and TNF receptor in the plasma membrane of infected cells, affects growth in host organisms. To determine whether the ability of poliovirus 3A to inhibit ER-to-Golgi traffic is conserved, the ability of 3A proteins from several picornaviruses, including human rhinovirus 14, foot-and-mouth disease virus, enterovirus 71, hepatitis A, and Theiler's virus, was tested. Only the 3A proteins from another poliovirus, Sabin 3, and closely related coxsackievirus B3 inhibited ER-to-Golgi traffic as effectively as the 3A protein from poliovirus Mahoney type 1. Site-directed mutagenesis based on these findings and the three-dimensional structure of the amino-terminal domain of poliovirus 3A protein revealed that residues in the unstructured amino terminus of 3A are critical for the inhibition of host protein secretion.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305-5127, USA.
authors.forename: Sunny S
authors.initials: SS
authors.lastname: Choe
authors.forename: Dana A
authors.initials: DA
authors.lastname: Dodd
authors.forename: Karla
authors.initials: K
authors.lastname: Kirkegaard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D006056:Golgi Apparatus / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D017955:Poliovirus / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D014758:Viral Core Proteins / Q000494:pharmacology*
chemical_list: C109349:3A protein, Poliovirus; D011506:Proteins; D014758:Viral Core Proteins