Amphipathic helix-dependent localization of NS5A mediates hepatitis C virus RNA replication.
We identified an N-terminal amphipathic helix (AH) in one of hepatitis C virus (HCV)'s nonstructural proteins, NS5A. This AH is necessary and sufficient for membrane localization and is conserved across isolates. Genetically disrupting the AH impairs HCV replication. Moreover, an AH peptide-mimic inhibits the membrane association of NS5A in a dose-dependent manner. These results have exciting implications for the HCV life cycle and novel antiviral strategies.
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California 94305, USA.
Menashe
M
Elazar
Kwang Ho
KH
Cheong
Ping
P
Liu
Harry B
HB
Greenberg
Charles M
CM
Rice
Jeffrey S
JS
Glenn
D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D017124:Conserved Sequence; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D012367:RNA, Viral / Q000096:biosynthesis*; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
D010455:Peptides; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase