| Full text | |
| Author(s): |
Ward, Joseph C.
[1, 2]
;
Bowyer, Sebastian
[1, 2]
;
Chen, Shucheng
[1, 2]
;
Campos, Guilherme Rodrigues Fernandes
[1, 2, 3]
;
Ramirez, Santseharay
[4, 5]
;
Bukh, Jens
[4, 5]
;
Harris, Mark
[1, 2]
Total Authors: 7
|
| Affiliation: | [1] Univ Leeds, Fac Biol Sci, Sch Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire - England
[2] Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire - England
[3] Sao Paulo State Univ, Inst Biosci Languages & Exact Sci, Cristovao Colombo St 2265, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[4] Hvidovre Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis C Program CO HEP, Kettegard Alle 30, DK-2650 Hvidovre - Denmark
[5] Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Blegdamsvej 3, DK-2200 Copenhagen N - Denmark
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | JOURNAL OF GENERAL VIROLOGY; v. 101, n. 11, p. 1182-1190, 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
Hepatitis C virus (HCV) is an important human pathogen causing 400 000 chronic liver disease-related deaths annually. Until recently, the majority of laboratory-based investigations into the biology of HCV have focused on the genotype 2 isolate, JFH-1, involving replicons and infectious cell culture systems. However, genotype 2 is one of eight major genotypes of HCV and there is great sequence variation among these genotypes (>30% nucleotide divergence). In this regard, genotype 3 is the second most common genotype and accounts for 30% of global HCV cases. Further, genotype 3 is associated with both high levels of inherent resistance to direct-acting antiviral (DAA) therapy, and a more rapid progression to chronic liver diseases. Neither of these two attributes are fully understood, thus robust genotype 3 culture systems to unravel viral replication are required. Here we describe the generation of robust genotype 3 sub-genomic replicons (SGRs) based on the adapted HCV NS3-NS5B replicase from the DBN3a cell culture infectious clone. Such infectious cell culture-adaptive mutations could potentially promote the development of robust SGRs for other HCV strains and genotypes. The novel genotype 3 SGRs have been used both transiently and to establish stable SGR-harbouring cell lines. We show that these resources can be used to investigate aspects of genotype 3 biology, including NS5A function and DAA resistance. They will be useful tools for these studies, circumventing the need to work under the biosafety level 3 (BSL3) containment required in many countries. (AU) | |
| FAPESP's process: | 16/03807-0 - Study of resistance mutations to treatment with Directly Acting antivirals in patients infected with hepatitis C virus genotype 3 |
| Grantee: | Guilherme Rodrigues Fernandes Campos |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 18/04678-5 - Analysis of Hepatitis C virus genotype 3 resistance to direct acting antivirals |
| Grantee: | Guilherme Rodrigues Fernandes Campos |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |