A replicon-based shuttle vector system for assessing the phenotype of HCV NS5B polymerase genes isolated from patient populations.

A replicon-based shuttle vector system for assessing the phenotype of HCV NS5B polymerase genes isolated from patient populations. Research Abstract Details 

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A replicon-based shuttle vector system for assessing the phenotype of HCV NS5B polymerase genes isolated from patient populations. Abstract Text:

Tim Middleton,Yupeng He,Tami Pilot-Matias,Rakesh Tripathi,Ben Hock Lim,Andrew Roth,Chih-Ming Chen,Gennadiy Koev,Teresa I Ng,Preethi Krishnan,Ron Pithawalla,Rubina Mondal,Tatyana Dekhtyar,Liangjun Lu,Hongmei Mo,Warren M Kati,Akhteruzzaman Molla,Tim Middleton,Yupeng He,Tami Pilot-Matias,Rakesh Tripathi,Ben Hock Lim,Andrew Roth,Chih-Ming Chen,Gennadiy Koev,Teresa I Ng,Preethi Krishnan,Ron Pithawalla,Rubina Mondal,Tatyana Dekhtyar,Liangjun Lu,Hongmei Mo,Warren M Kati,Akhteruzzaman Molla,

Hepatitis C virus (HCV) replicon-based shuttle vectors that permit phenotypes of NS5B polymerase genes from a large number of patient isolates to be rapidly assessed when transiently expressed in cultured cells were designed. When used to test responses to an inhibitor of HCV RNA-dependent RNA polymerase, IC(50) values for inhibition covered a several hundred-fold range among 47 patient samples tested. This observation highlights the variability that can be found by testing isolates derived from HCV-infected subjects. Partial suppression with a polymerase inhibitor of the most sensitive species permitted detection of minor quasispecies that were 7-200-fold more resistant than the bulk population in approximately half of the samples. Sequence analysis showed a wide range of amino acid changes not detected by conventional selection methods using laboratory-derived strains. This approach provides a means to assess variation in antiviral efficacy, and to predict possible responses in a clinical setting.

A replicon-based shuttle vector system for assessing the phenotype of HCV NS5B polymerase genes isolated from patient populations. Publishing Authors By Initials

T Middleton,Y He,T Pilot-Matias,R Tripathi,BH Lim,A Roth,CM Chen,G Koev,TI Ng,P Krishnan,R Pithawalla,R Mondal,T Dekhtyar,L Lu,H Mo,WM Kati,A Molla,T Middleton,Y He,T Pilot-Matias,R Tripathi,BH Lim,A Roth,CM Chen,G Koev,TI Ng,P Krishnan,R Pithawalla,R Mondal,T Dekhtyar,L Lu,H Mo,WM Kati,A Molla,

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A replicon-based shuttle vector system for assessing the phenotype of HCV NS5B polymerase genes isolated from patient populations. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of virological methods

VOLUME: 145

Page Numbers: 137-45

Journal Abbreviation: J. Virol. Methods

ISSN: 0166-0934

DAY: 29

MONTH: 06

YEAR: 2007

A replicon-based shuttle vector system for assessing the phenotype of HCV NS5B polymerase genes isolated from patient populations. Information

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LANGUAGE: eng

NlmUniqueID: 8005839

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Grant and Affiliation Information for A replicon-based shuttle vector system for assessing the phenotype of HCV NS5B polymerase genes isolated from patient populations.

AFFILIATION: Abbott Laboratories, Global Pharmaceutical Research and Development, Department R4CQ, AP52N, 200 Abbott Park Road, Abbott Park, IL 60064, USA. timothy.middleton@abbott.com

Country: Netherlands

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MEDLINETA: J Virol Methods

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