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Frequent compartmentalization of hepatitis C virus variants in circulating B cells and monocytes
Author(s) -
Ducoulombier Delphine,
RoqueAfonso AnneMarie,
Di Liberto Gaëtana,
Penin François,
Kara Rachid,
Richard Yolande,
Dussaix Elisabeth,
Féray Cyrille
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20087
Subject(s) - viral quasispecies , cd19 , biology , cd14 , hepatitis c virus , virology , antibody , hbsag , cd8 , virus , immunology , flow cytometry , microbiology and biotechnology , antigen , hepatitis b virus
Abstract Differences in the composition of the hepatitis C virus (HCV) quasispecies between plasma and blood mononuclear cells (BMC) strongly suggest that BMCs support viral replication. We examined the frequency of such compartmentalization, the cell types involved, the constraints exerted on the different variants, and the role of immunoglobulin‐complexed variants. We screened the hypervariable region (HVR1) of HCV isolates from 14 HBsAg ‐ and HIV‐seronegative patients with chronic HCV infection. HCV RNA was amplified and cloned from plasma, the immunoglobulin G (IgG)‐bound fraction, and total and sorted BMCs (CD19+, CD8+, CD4+, and CD14+ cells). Compartmentalization was estimated using a matrix correlation test. The ratio of nonsynonymous/synonymous substitutions (d N /d S ratio) was calculated for each compartment. HCV RNA was detected in 3/3 BMC, 11/11 CD19+, 10/11 CD14+, 4/11 CD8+ and 0/11 CD4+ cell samples. HVR1 sequences were significantly different between plasma and at least one cellular compartment in all nine cases analyzed, and between B cells (CD19+) and monocytes (CD14+) in all five available cases. IgG‐bound variants were distinct from cellular variants. D N /d S ratios were similar (n = 3) or lower (n = 6) in cellular compartments compared with plasma and the IgG‐bound fraction. In conclusion, HCV compartmentalization is a common phenomenon. B cells and monocytes harbor HCV variants showing a low rate of nonsynonymous mutations, a feature that might contribute to the persistence of HCV infection. (H EPATOLOGY 2004;39:817–825.)