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

Hdl Handle:
http://hdl.handle.net/10147/209289
Title:
Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile.
Authors:
Moreau, Isabelle; O'Sullivan, Hilary; Murray, Caroline; Levis, John; Crosbie, Orla; Kenny-Walsh, Elizabeth; Fanning, Liam J
Affiliation:
Department of Medicine, Molecular Virology Diagnostic & Research Laboratory,, Clinical Sciences Building, Cork University Hospital, Cork, Ireland., i.moreau@ucc.ie
Citation:
Virol J. 2008 Sep 23;5:103.
Journal:
Virology journal
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209289
DOI:
10.1186/1743-422X-5-103
PubMed ID:
18811965
Abstract:
BACKGROUND: 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.
Language:
eng
MeSH:
Amino Acid Sequence; Genotype; Hepacivirus/classification/*genetics/immunology/*isolation & purification; Hepatitis C/*immunology/virology; Hepatitis C Antibodies/*immunology; Humans; Immunoglobulin G/*immunology; Molecular Sequence Data; Mutagenesis, Insertional; Phylogeny; Sequence Alignment
ISSN:
1743-422X (Electronic); 1743-422X (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMoreau, Isabelleen_GB
dc.contributor.authorO'Sullivan, Hilaryen_GB
dc.contributor.authorMurray, Carolineen_GB
dc.contributor.authorLevis, Johnen_GB
dc.contributor.authorCrosbie, Orlaen_GB
dc.contributor.authorKenny-Walsh, Elizabethen_GB
dc.contributor.authorFanning, Liam Jen_GB
dc.date.accessioned2012-02-03T15:17:18Z-
dc.date.available2012-02-03T15:17:18Z-
dc.date.issued2012-02-03T15:17:18Z-
dc.identifier.citationVirol J. 2008 Sep 23;5:103.en_GB
dc.identifier.issn1743-422X (Electronic)en_GB
dc.identifier.issn1743-422X (Linking)en_GB
dc.identifier.pmid18811965en_GB
dc.identifier.doi10.1186/1743-422X-5-103en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209289-
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_GB
dc.language.isoengen_GB
dc.subject.meshAmino Acid Sequenceen_GB
dc.subject.meshGenotypeen_GB
dc.subject.meshHepacivirus/classification/*genetics/immunology/*isolation & purificationen_GB
dc.subject.meshHepatitis C/*immunology/virologyen_GB
dc.subject.meshHepatitis C Antibodies/*immunologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunoglobulin G/*immunologyen_GB
dc.subject.meshMolecular Sequence Dataen_GB
dc.subject.meshMutagenesis, Insertionalen_GB
dc.subject.meshPhylogenyen_GB
dc.subject.meshSequence Alignmenten_GB
dc.titleSeparation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile.en_GB
dc.contributor.departmentDepartment of Medicine, Molecular Virology Diagnostic & Research Laboratory,, Clinical Sciences Building, Cork University Hospital, Cork, Ireland., i.moreau@ucc.ieen_GB
dc.identifier.journalVirology journalen_GB
dc.description.provinceMunster-

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