Hepatitis C virus NS5A protein modulates template selection by the RNA polymerase in in vitro system.
Hepatitis C virus (HCV) NS5A phosphoprotein is a component of virus replicase. Here we demonstrate that in vitro unphosphorylated NS5A protein inhibits HCV RNA-dependent RNA polymerase (RdRp) activity in polyA-oligoU system but has little effect on synthesis of viral RNA. The phosphorylated casein kinase (CK) II NS5A protein causes the opposite effect on RdRp in each of these systems. The phosphorylation of NS5A protein with CKII does not affect its affinity to the HCV RdRp and RNA. The NS5A phosphorylation with CKI does not change the RdRp activity. Herein we report evidence that the NS5A prevents template binding to the RdRp.
Ivanov
Alexander V
AV
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov street, 32, Moscow 119991, Russia. aivanov@yandex.ru
Tunitskaya
Vera L
VL
Ivanova
Olga N
ON
Mitkevich
Vladimir A
VA
Prassolov
Vladimir S
VS
Makarov
Alexander A
AA
Kukhanova
Marina K
MK
Kochetkov
Sergey N
SN
D047390:Casein Kinase II / Q000378:metabolism; D002460:Cell Line; D016174:Hepacivirus / Q000201:enzymology / Q000502:physiology; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D013698:Templates, Genetic; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication
D010750:Phosphoproteins; D017361:Viral Nonstructural Proteins; D047390:Casein Kinase II; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase