title: Analysis of a non-structural gene reveals evidence of possible hepatitis C virus (HCV) compartmentalization.
abstract: Viral diversity is a hallmark of hepatitis C virus (HCV) infection; however, only limited data are available regarding HCV variability in extrahepatic sites, and none have systematically compared diversity in non-structural and structural genomic regions. Therefore, HCV diversity in the NS5B and envelope 1 (E1) hypervariable region 1 (HVR1) genes was evaluated in matched sera and peripheral blood mononuclear cells (PBMCs) obtained from 13 HCV-infected women. Multiple clonal sequences were compared to evaluate quasispecies diversity and viral compartmentalization in PBMCs. Genetic distances were higher for E1/HVR1 compared to NS5B in both the sera and PBMCs (P = 0.0511 and 0.0284). Genetic distances were higher in serum NS5B compared to PBMC NS5B (P = 0.0003); however, they were not different when comparing E1/HVR1 in sera to PBMCs. By phylogenetic analysis of NS5B, evidence of possible PBMC compartmentalization was observed for one woman, while statistical methods were consistent with PBMC compartmentalization for six women. Evidence of compartmentalization within a non-structural genomic region may suggest that viral adaptation to a unique extracellular microenvironment(s) may be required for efficient replication and could contribute to HCV persistence.
authors.affiliation: Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. jason.blackard@uc.edu
authors.forename: Jason T
authors.initials: JT
authors.lastname: Blackard
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Welge
authors.forename: Christina M
authors.initials: CM
authors.lastname: Martin
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Taylor
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Mayer
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Jamieson
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D005260:Female; D014644:Genetic Variation; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008875:Middle Aged; D010802:Phylogeny; D020539:Sequence Analysis, Protein; D014759:Viral Envelope Proteins / Q000097:blood / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000097:blood / Q000235:genetics*; D055815:Young Adult; D012324:RNA-Dependent RNA Polymerase
chemical_list: D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C087035:E1 protein, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase