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Article: High-resolution functional profiling of hepatitis C virus genome

TitleHigh-resolution functional profiling of hepatitis C virus genome
Authors
Issue Date2008
Citation
PLoS Pathogens, 2008, v. 4, n. 10, article no. e1000182 How to Cite?
AbstractHepatitis C virus is a leading cause of human liver disease worldwide. Recent discovery of the JFH-1 isolate, capable of infecting cell culture, opens new avenues for studying HCV replication. We describe the development of a high-throughput, quantitative, genome-scale, mutational analysis system to study the HCV cis-elements and protein domains that are essential for virus replication. An HCV library with 15-nucleotide random insertions was passaged in cell culture to examine the effect of insertions at each genome location by insertion-specific fluorescent-PCR profiling. Of 2399 insertions identified in 9517 nucleotides of the genome, 374, 111, and 1914 were tolerated, attenuating, and lethal, respectively, for virus replication. Besides identifying novel functional domains, this approach confirmed other functional domains consistent with previous studies. The results were validated by testing several individual mutant viruses. Furthermore, analysis of the 3′ non-translated variable region revealed a spacer role in virus replication, demonstrating the utility of this approach for functional discovery. The high-resolution functional profiling of HCV domains lays the foundation for further mechanistic studies and presents new therapeutic targets as well as topological information for designing vaccine candidates. © 2008 Arumugaswami et al.
Persistent Identifierhttp://hdl.handle.net/10722/285640
ISSN
2020 Impact Factor: 6.823
2020 SCImago Journal Rankings: 3.719
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorArumugaswami, Vaithilingaraja-
dc.contributor.authorRemenyi, Roland-
dc.contributor.authorKanagavel, Vidhya-
dc.contributor.authorSue, Eric Yiang-
dc.contributor.authorHo, Tuyet Ngoc-
dc.contributor.authorLiu, Chang-
dc.contributor.authorFontanes, Vanessa-
dc.contributor.authorDasgupta, Asim-
dc.contributor.authorSun, Ren-
dc.date.accessioned2020-08-18T04:56:16Z-
dc.date.available2020-08-18T04:56:16Z-
dc.date.issued2008-
dc.identifier.citationPLoS Pathogens, 2008, v. 4, n. 10, article no. e1000182-
dc.identifier.issn1553-7366-
dc.identifier.urihttp://hdl.handle.net/10722/285640-
dc.description.abstractHepatitis C virus is a leading cause of human liver disease worldwide. Recent discovery of the JFH-1 isolate, capable of infecting cell culture, opens new avenues for studying HCV replication. We describe the development of a high-throughput, quantitative, genome-scale, mutational analysis system to study the HCV cis-elements and protein domains that are essential for virus replication. An HCV library with 15-nucleotide random insertions was passaged in cell culture to examine the effect of insertions at each genome location by insertion-specific fluorescent-PCR profiling. Of 2399 insertions identified in 9517 nucleotides of the genome, 374, 111, and 1914 were tolerated, attenuating, and lethal, respectively, for virus replication. Besides identifying novel functional domains, this approach confirmed other functional domains consistent with previous studies. The results were validated by testing several individual mutant viruses. Furthermore, analysis of the 3′ non-translated variable region revealed a spacer role in virus replication, demonstrating the utility of this approach for functional discovery. The high-resolution functional profiling of HCV domains lays the foundation for further mechanistic studies and presents new therapeutic targets as well as topological information for designing vaccine candidates. © 2008 Arumugaswami et al.-
dc.languageeng-
dc.relation.ispartofPLoS Pathogens-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleHigh-resolution functional profiling of hepatitis C virus genome-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.ppat.1000182-
dc.identifier.pmid18927624-
dc.identifier.pmcidPMC2564836-
dc.identifier.scopuseid_2-s2.0-55449118911-
dc.identifier.volume4-
dc.identifier.issue10-
dc.identifier.spagearticle no. e1000182-
dc.identifier.epagearticle no. e1000182-
dc.identifier.eissn1553-7374-
dc.identifier.isiWOS:000261481100015-
dc.identifier.issnl1553-7366-

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