Imperial College London
Portrait Picture

Dr Josh Wong

Faculty of Natural Sciences, Department of Life Sciences

Scientific Lead
 
 
 
//

Contact

 

+44 (0)20 7594 5300joshua.wong

 
 
//

Location

 

210Sir Ernst Chain BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Cunningham:2015:10.1002/hep.27570,
author = {Cunningham, ME and Javaid, A and Waters, J and DavidsonWright, J and Wong, JLC and Jones, M and Foster, GR},
doi = {10.1002/hep.27570},
journal = {Hepatology},
pages = {1192--1204},
title = {Development and validation of a “capturefusion” model to study drug sensitivity of patientderived hepatitis C},
url = {http://dx.doi.org/10.1002/hep.27570},
volume = {61},
year = {2015}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:p>Emerging therapies for chronic hepatitis C viral (HCV) infection involve inhibition of viral enzymes with drug combinations. Natural, or treatmentinduced, enzyme polymorphisms reduce efficacy. We developed a phenotyping assay to aid drug selection based on viral transfer from monocytes to hepatocytes. We studied HCV in monocytes from infected patients and developed a model in which patientderived HCV is “captured” by the cell line THP1 and replication assessed after fusion to hepatoma cells. We found that monocytes from HCVinfected patients harbor virus that replicates when cells are fused to hepatocytes. THP1 cells incubated with infected sera capture HCV, which replicates when fused to hepatocytes. Inhibitable replication of all HCV genotypes was achieved (42 of 52 isolates). We measured sensitivity of telaprevir (TVR) and alisporivir (AVR) in different genotypes, and showed differences in 50% inhibitory concentration (IC<jats:sub>50</jats:sub>) correlating with clinical response (TVR IC<jats:sub>50</jats:sub> for genotype (G)1 was 0.042 ± 0.003 vs. 0.117 ± 0.015 μM for G3, whereas AVR IC<jats:sub>50</jats:sub> for G1 was 0.139 ± 0.013 vs. 0.044 ± 0.007 μM for G3). We tested TVRresistant viral isolates and identified changes in IC<jats:sub>50</jats:sub>. One patient with a poor clinical response to TVR and wildtype viral sequence showed reduced TVR sensitivity in our assay. We studied samples from a 2week TVR monotherapy study in which 5 of 8 patients with G3 HCV did not respond whereas 3 of 8 patients did. The “capturefusion” assay correctly identified responders. <jats:italic toggle="yes">Conclusion</jats:italic>: The capturefusion model represents a promising new technique that may help identify appropriate treatment strategies for patients with chronic HCV infection. (H<jats:sc>epatology</jats:sc> 2
AU  - Cunningham,ME
AU  - Javaid,A
AU  - Waters,J
AU  - DavidsonWright,J
AU  - Wong,JLC
AU  - Jones,M
AU  - Foster,GR
DO  - 10.1002/hep.27570
EP  - 1204
PY  - 2015///
SN  - 0270-9139
SP  - 1192
TI  - Development and validation of a “capturefusion” model to study drug sensitivity of patientderived hepatitis C
T2  - Hepatology
UR  - http://dx.doi.org/10.1002/hep.27570
VL  - 61
ER  -
Download