TY - JOUR
T1 - HCV NS5A co-operates with PKR in modulating HCV IRES-dependent translation
AU - Karamichali, Eirini
AU - Foka, Pelagia
AU - Tsitoura, Eliza
AU - Kalliampakou, Katerina
AU - Kazazi, Dorothea
AU - Karayiannis, Peter
AU - Georgopoulou, Urania
AU - Mavromara, Penelope
PY - 2014
Y1 - 2014
N2 - Translation initiation of the Hepatitis C virus (HCV) genome is driven by an internal ribosome entry site (IRES), located within the 5' non-coding region. Several studies have suggested that different cellular non canonical proteins or viral proteins can regulate the HCV IRES activity. However, the role of the viral proteins on HCV translation remains controversial. In this report, we confirmed previous studies showing that NS5A down-regulates IRES activity in HepG2 but not in Huh7 cells suggesting that the NS5A effect on HCV IRES is cell-type dependent. Additionally, we provide strong evidence that activated PKR up-regulates the IRES activity while silencing of endogenous PKR had the opposite effect. Furthermore, we present data indicating that the NS5A-mediated inhibitory effect on IRES-dependent translation could be linked with the PKR inactivation. Finally, we show that NS5A from GBV-C but not from GBV-B down-regulates HCV IRES activity in the absence or the presence of PKR over expression. Notably, HCV and GBV-C but not GBV-B NS5A contains a previously identified PKR interacting protein domain.
AB - Translation initiation of the Hepatitis C virus (HCV) genome is driven by an internal ribosome entry site (IRES), located within the 5' non-coding region. Several studies have suggested that different cellular non canonical proteins or viral proteins can regulate the HCV IRES activity. However, the role of the viral proteins on HCV translation remains controversial. In this report, we confirmed previous studies showing that NS5A down-regulates IRES activity in HepG2 but not in Huh7 cells suggesting that the NS5A effect on HCV IRES is cell-type dependent. Additionally, we provide strong evidence that activated PKR up-regulates the IRES activity while silencing of endogenous PKR had the opposite effect. Furthermore, we present data indicating that the NS5A-mediated inhibitory effect on IRES-dependent translation could be linked with the PKR inactivation. Finally, we show that NS5A from GBV-C but not from GBV-B down-regulates HCV IRES activity in the absence or the presence of PKR over expression. Notably, HCV and GBV-C but not GBV-B NS5A contains a previously identified PKR interacting protein domain.
KW - GBV-B NS5A
KW - GBV-C NS5A
KW - HCV IRES
KW - HCV NS5A
KW - PKR
KW - Translation
UR - http://www.scopus.com/inward/record.url?scp=84901756689&partnerID=8YFLogxK
U2 - 10.1016/j.meegid.2014.04.015
DO - 10.1016/j.meegid.2014.04.015
M3 - Article
C2 - 24815730
AN - SCOPUS:84901756689
SN - 1567-1348
VL - 26
SP - 113
EP - 122
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
ER -