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.
Elazar
Menashe
M
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California 94305, USA.
Cheong
Kwang Ho
KH
Liu
Ping
P
Greenberg
Harry B
HB
Rice
Charles M
CM
Glenn
Jeffrey S
JS
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