title: Genetic heterogeneity of the hypervariable region I of Hepatitis C virus and lymphoproliferative disorders.
abstract: B-cell lymphoproliferative disorders (BCLD) have been associated with chronic hepatitis C virus (HCV) infection. The HCV glycoprotein E2 (gpE2) hypervariable region I (HVR-I) may be a potential antigenic candidate to promote B-cell proliferation. The purpose of this study was to analyze the influence of HVR-I sequence variability in the development of BCLD. HVR-I sequences were studied in 29 chronically HCV-infected patients with (n=15) or without (n=14) BCLD. After PCR amplification of the gpE2 region, analysis of the 81 bp HVR-I encoding fragment was performed on 7-18 clones per patient. HVR-I sequence complexity was slightly lower in patients with BCLD (mean 0.347) than without (0.468) (P=0.2), though, sequence diversities were similar (0.0370 vs 0.0954, P=0.239). Phylogenetic analysis did not reveal any BCLD-associated clustering. In our population, neither the recently described insertion between positions 1 and 2 of HVR-I nor residues at positions 4 and 13 were particularly linked to BCLD. As previously described, we confirm the high degree of conservation of HVR-I residues T-2, G-6 and G-23 in our patients. Contrary to recent findings, our analysis based on multiple clones per patient analysis did not reveal any particular motif associated with BCLD.
authors.affiliation: Virology Laboratory, Hopital Pitie-Salpetriere, 75651 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Rigolet
authors.forename: P
authors.initials: P
authors.lastname: Cacoub
authors.forename: A
authors.initials: A
authors.lastname: Schnuriger
authors.forename: L
authors.initials: L
authors.lastname: Vallat
authors.forename: A
authors.initials: A
authors.lastname: Cahour
authors.forename: P
authors.initials: P
authors.lastname: Ghillani
authors.forename: F
authors.initials: F
authors.lastname: Davi
authors.forename: Y
authors.initials: Y
authors.lastname: Benhamou
authors.forename: J-C
authors.initials: JC
authors.lastname: Piette
authors.forename: V
authors.initials: V
authors.lastname: Thibault
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D018740:Genetic Heterogeneity; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000821:virology*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D014759:Viral Envelope Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*
chemical_list: C400562:HVR1 protein, Hepatitis C virus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C091015:glycoprotein E2, Hepatitis C virus