title: A new type of intracellular retention signal identified in a pestivirus structural glycoprotein.
abstract: Sorting of membrane proteins into intracellular organelles is crucial for cell function. Viruses exploit intracellular transport and retention systems to concentrate envelope proteins at the site of virus budding. In pestiviruses, a group of important pathogens of pigs and ruminants closely related to human hepatitis C virus, the E(rns) protein translated from the viral RNA is secreted from the infected cells and found in the serum of infected animals. Secretion of the protein is regarded as crucial for its function as a viral virulence factor associated with its RNase activity. However, ∼95% of the E(rns) molecules are retained within the infected cell. Fusion of different E(rns) fragments to the C terminus of CD72 allowed identification of a retention signal within the C-terminal 65 aa of the viral protein. This C-terminal sequence represents its membrane anchor and folds into an amphipathic helix binding in-plane to the membrane surface. Residues L183, I190, and L208 are important for intracellular location of E(rns). Presentation of the retention signal on the cytoplasmic instead of the luminal face of the ER membrane in CD8α fusion proteins still led to retention. Thus, E(rns) contains in its C-terminal amphipathic helix an intracellular retention signal that is active on both faces of the membrane.
authors.affiliation: Institut für Immunologie, Friedrich-Loeffler-Institut, Insel Riems, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Burrack
authors.forename: Daniel
authors.initials: D
authors.lastname: Aberle
authors.forename: Jochen
authors.initials: J
authors.lastname: Bürck
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.forename: Gregor
authors.initials: G
authors.lastname: Meyers
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D002478:Cells, Cultured; D006692:Classical Swine Fever Virus / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010576:Pestivirus / Q000235:genetics*; D017433:Protein Structure, Secondary; D021381:Protein Transport / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C466501:E(rns) protein, classic swine fever virus; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins