title: Analysis of hepatitis C virus hypervariable region 1 sequence from cryoglobulinemic patients and associated controls.
abstract: Chronic hepatitis C virus (HCV) infection is frequently associated with extrahepatic manifestations, including nonmalignant and malignant B-cell lymphoproliferative disorders. It has been reported that specific changes or recurring motifs in the amino acid sequence of the HCV hypervariable region 1 (HVR1) may be associated with cryoglobulinemia. We searched for specific insertions/deletions and/or amino acid motifs within HVR1 in samples from 80 symptomatic and asymptomatic patients with and 33 patients without detectable cryoglobulins, all with chronic HCV infection. At variance with the results of a previous study which reported a high frequency of insertions at position 385 of HVR1 from cryoglobulinemic patients, we found a 6.2% prevalence of insertions in samples from patients with and a 9.1% prevalence in those without cryoglobulinemia. Moreover, statistical and bioinformatics approaches including Fisher's exact test, k-means clustering, Tree determinant-residue identification, correlation of mutations, principal component analysis, and phylogenetic analysis failed to show statistically significant differences between sequences from cryoglobulin-negative and -positive patients. Our findings suggest that cryoglobulinemia may arise by virtue of as-yet-unidentified host- rather than virus-specific factors. Specific changes in HCV envelope sequence distribution are unlikely to be directly involved in the establishment of pathological B-cell monoclonal proliferation.
authors.affiliation: Area Infettivologica, Dipartimento di Malattie Infettive, IRCCS Policlinico San Matteo, Via Taramelli 5, 27100 Pavia, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Bianchettin
authors.forename: Claudia
authors.initials: C
authors.lastname: Bonaccini
authors.forename: Romina
authors.initials: R
authors.lastname: Oliva
authors.forename: Anna
authors.initials: A
authors.lastname: Tramontano
authors.forename: Agostino
authors.initials: A
authors.lastname: Cividini
authors.forename: Milvia
authors.initials: M
authors.lastname: Casato
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.forename: Enrico
authors.initials: E
authors.lastname: Silini
authors.forename: Mario U
authors.initials: MU
authors.lastname: Mondelli
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D016000:Cluster Analysis; D019295:Computational Biology; D003449:Cryoglobulinemia / Q000235:genetics*; D017931:DNA Primers; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D007558:Italy; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010802:Phylogeny; D025341:Principal Component Analysis; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; C400562:HVR1 protein, Hepatitis C virus; D014764:Viral Proteins