geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Effect of interaction between hepatitis C virus NS5A and NS5B on hepatitis C virus RNA replication with the hepatitis C virus replicon


, : Effect of interaction between hepatitis C virus NS5A and NS5B on hepatitis C virus RNA replication with the hepatitis C virus replicon. Journal of Virology 78(6): 2738-2748

Hepatitis C virus (HCV) NS5A has been reported to be important for the establishment of replication by adaptive mutations or localization, although its role in viral replication remains unclear. It was previously reported that NS5A interacts with NS5B via two regions of NS5A in the isolate JK-1 and modulates the activity of NS5B RdRp (Y. Shirota et al., J. Biol. Chem., 277:11149-11155, 2002), but the biological significance of this interaction has not been determined. In this study, we addressed the effect of this interaction on HCV RNA replication with an HCV replicon system derived from the isolate M1LE (H. Kishine et al., Biochem. Biophys. Res. Commun., 293:993-999, 2002). We constructed three internal deletion mutants, M1LE/5Adel-1 and M1LE/5Adel-2, each encoding NS5A which cannot bind NS5B, and M1LE/5Adel-3, encoding NS5A that can bind NS5B. After transfection into Huh-7 cells, M1LE/5Adel-3 was replication competent, but both M1LE/5Adel-1 and M1LE/5Adel-2 were not. Next we prepared 20 alanine-substituted clustered mutants within both NS5B-binding regions and examined the effect of these mutants on HCV RNA replication. Only 5 of the 20 mutants were replication competent. Subsequently, we introduced a point mutation, S225P, a deletion of S229, or S2321 into NSSA and prepared cured Huh-7 cells that were cured of RNA replication by alpha interferon. Finally, with these point mutations and cured cells, we established a highly improved replicon system. In this system, only the same five mutants were replication competent. These results strongly suggest that the interaction between NS5A and NSSB is critical for HCV RNA replication in the HCV replicon system.

US$19.90

PMID: 14990694

DOI: 10.1128/JVI.78.6.2738-2748.2004


Other references

Saito Naoki; Coifman Ronald R., 1997: Extraction of geological information from acoustic well-logging waveforms using time-frequency wavelets. Recently developed classification and regression methods are applied to extract geological information from acoustic well-logging waveforms. First, acoustic waveforms are classified into the ones propagated through sandstones and the ones propagat...

Schulte-Wrede, S.; Wetzstein, R., 1972: Scanning electron microscopy of spermatozoa of the domestic sheep (Ovis ammon aries, L.). The detailed appearance of sheep spermatozoa under the scanning electron microscopy is compared with that reported by other authors who had used the transmission electron microscope.

Anonymous, 1957: Latar orchardgrass for Pacific Northwest. Latar is late maturing, vigourous, winter-hardy and has a low lignin content. It makes good hay with lucerne in fertile well-watered areas. Resistance to leaf spot compares favourably with that of other varieties.

Mytnikov, A.M.; Smirnov, I.N.; Ivanov, L.B.; Eshankulov, G.S.; Bukhanov, V.E., 1989: Osteoscintigraphy in the evaluation of a bone transplant in cranioplasty in children. Scintigraphy of the skeleton with 99mTc-methylene diphosphonate was performed before operation and 3.6 and 12 mos. after allocranioplasty in 15 children aged 3 to 15 with posttraumatic defects of the bones of the cranial vault. Scintigraphic resul...

Gürbüz, F.; Ceylaner, S.; Topaloğlu, A.Kemal.; Yüksel, B., 2016: Crouzonodermoskeletal Syndrome with Hypoplasia of Corpus Callosum and Inferior Vermis. Journal of Clinical Research in Pediatric Endocrinology 8(3): 373-374

Struve, H.G., 1979: Observations on cereal fields after a hail storm. Illustrated descriptions of different forms of hail damage to rye, wheat and barley plants and ears, as well as estimates of the resultant yield loss, are given.

Tavares, Lélia.; Fortalezas, S.; Tyagi, M.; Barata, D.; Serra, A.Teresa.; Duarte, C.Maria.Martins.; Duarte, R.Oliveira.; Feliciano, R.Pedro.; Bronze, M.Rosário.; Espírito-Santo, M.Dalila.; Ferreira, R.Boavida.; Santos, Cáudia.Nunes., 2012: Bioactive compounds from endemic plants of Southwest Portugal: inhibition of acetylcholinesterase and radical scavenging activities. Natural products are reported to have substantial neuroprotective activity due to their radical scavenging capacity, and also acetylcholinesterase (AChE) inhibitory capacity, both activities important in neurodegeneration. The undesirable side eff...

Pearl M.; Taylor A., 1987: Microtubule networks visualized in isolated bladder epithelium from bufo marinus. Cell Biology International Reports 11(3): 242

Verine, A.; Salers, P.; Rouard, M.; Boyer, J., 1976: Analytical-scale isolation of triacylglycerol lipase from human adipose tissue. Febs Letters 66(1): 127-131

Osinska, B.; Nowakowska, H., 1991: Investigation on Polymyxa betae Keskin - vector of sugar beet rhizomania. Roczniki Nauk Rolniczych Seria E Ochrona Roslin. 1989( ); 191-2: 7-14