The N-terminal region of severe acute respiratory syndrome coronavirus protein 6 induces membrane rearrangement and enhances virus replication.
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.
Zhou
Haixia
H
Department of Microbiology, University of Iowa, 3-712 BSB, Iowa City, IA 52242, USA.
Ferraro
Debra
D
Zhao
Jincun
J
Hussain
Snawar
S
Shao
Jianqiang
J
Trujillo
Jonathan
J
Netland
Jason
J
Gallagher
Thomas
T
Perlman
Stanley
S
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
D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014764:Viral Proteins; C507223:protein 6, SARS virus