title: The N-terminal region of severe acute respiratory syndrome coronavirus protein 6 induces membrane rearrangement and enhances virus replication.
abstract: The severe acute respiratory syndrome coronavirus (SARS-CoV) accessory protein 6 (p6) is a 63-amino-acid multifunctional Golgi-endoplasmic reticulum (ER) membrane-associated protein, with roles in enhancing virus replication and in evading the innate immune response to infection by inhibiting STAT1 (signal transducer and activator of transcription factor 1) translocation to the nucleus. Here, we demonstrate that p6 has an N-terminal region-cytoplasm-C-terminal region-cytoplasm configuration with residues 2 to 37 likely membrane embedded. Expression of p6, or of its N-terminal 41-amino-acid region, in the absence of other viral proteins, induced the formation of membranous structures, some of which were similar to double membrane vesicles involved in virus replication. Consistent with a role in virus replication, p6 partially colocalized with nonstructural protein 3 (nsp3), a marker for virus replication complexes. Further, while the C-terminal region is required for preventing STAT1 translocation to the nucleus, our results also indicated that the N-terminal 18 amino acids were necessary for maximal inhibition. Collectively, these results support the notion that p6 is a two-domain protein, although the function of each is not completely independent of the other.
authors.affiliation: Department of Microbiology, University of Iowa, 3-712 BSB, Iowa City, IA 52242, USA.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhou
authors.forename: Debra
authors.initials: D
authors.lastname: Ferraro
authors.forename: Jincun
authors.initials: J
authors.lastname: Zhao
authors.forename: Snawar
authors.initials: S
authors.lastname: Hussain
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Shao
authors.forename: Jonathan
authors.initials: J
authors.lastname: Trujillo
authors.forename: Jason
authors.initials: J
authors.lastname: Netland
authors.forename: Thomas
authors.initials: T
authors.lastname: Gallagher
authors.forename: Stanley
authors.initials: S
authors.lastname: Perlman
mesh_terms: D021581:Active Transport, Cell Nucleus; D002462:Cell Membrane / Q000737:chemistry*; D002478:Cells, Cultured; D006801:Humans; D017433:Protein Structure, Secondary; D021381:Protein Transport; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000502:physiology*; D014779:Virus Replication
chemical_list: D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014764:Viral Proteins; C507223:protein 6, SARS virus