Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile

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dc.contributor.authorMoreau, Isabelle
dc.contributor.authorO'Sullivan, Hilary
dc.contributor.authorMurray, Caroline
dc.contributor.authorLevis, John
dc.contributor.authorCrosbie, Orla
dc.contributor.authorKenny-Walsh, Elizabeth
dc.contributor.authorFanning, Liam J.
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2013-01-26T17:00:36Z
dc.date.available2013-01-26T17:00:36Z
dc.date.copyright2008
dc.date.issued2008-08
dc.date.updated2013-01-18T10:50:14Z
dc.description.abstractBackground: Hepatitis C virus (HCV) circulates in an infected individual as a heterogeneous mixture of closely related viruses called quasispecies. The E1/E2 region of the HCV genome is hypervariable (HVR1) and is targeted by the humoral immune system. Hepatitis C virions are found in two forms: antibody associated or antibody free. The objective of this study was to investigate if separation of Hepatitis C virions into antibody enriched and antibody depleted fractions segregates quasispecies populations into distinctive swarms. Results: A HCV genotype 4a specimen was fractionated into IgG-depleted and IgG-enriched fractions by use of Albumin/IgG depletion spin column. Clonal analysis of these two fractions was performed and then compared to an unfractionated sample. Following sequence analysis it was evident that the antibody depleted fraction was significantly more heterogeneous than the antibody enriched fraction, revealing a unique quasispecies profile. An in-frame 3 nt insertion was observed in 26% of clones in the unfractionated population and in 64% of clones in the IgG-depleted fraction. In addition, an in-frame 3 nt indel event was observed in 10% of clones in the unfractionated population and in 9% of clones in the IgG-depleted fraction. Neither of these latter events, which are rare occurrences in genotype 4a, was identified in the IgG-enriched fraction.Conclusion: In conclusion, the homogeneity of the IgG-enriched species is postulated to represent a sequence that was strongly recognised by the humoral immune system at the time the sample was obtained. The heterogeneous nature of the IgG-depleted fraction is discussed in the context of humoral escape.en
dc.description.sponsorshipHealth Research Board (505-005-711-4912)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMoreau, I, O'Sullivan, H, Murray, C, Levis, J, Crosbie, O, Kenny-Walsh, E, Fanning, LJ (2008) 'Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile'. Virology Journal, 5:103. doi: 10.1186/1743-422X-5-103en
dc.identifier.doi10.1186/1743-422X-5-103
dc.identifier.issn1743-422X
dc.identifier.journaltitleVirology Journalen
dc.identifier.urihttps://hdl.handle.net/10468/928
dc.identifier.volume5en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urihttp://www.virologyj.com/content/5/1/103
dc.rights© 2008 Moreau et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/en
dc.subjectHypervariable region-1en
dc.subjectNeutralising antibodiesen
dc.subjectAntiviral therapyen
dc.subjectLow-densityen
dc.subjectLife-cycleen
dc.subjectVirusen
dc.subjectInfectionen
dc.subjectRecombinanten
dc.subjectEnhancementen
dc.subjectParticlesen
dc.subject.lcshHepatitis C virusen
dc.subject.lcshImmune systemen
dc.subject.lcshAntibodiesen
dc.titleSeparation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profileen
dc.typeArticle (peer-reviewed)en
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