A possible role of hypervariable region 1 quasispecies in escape of hepatitis C virus particles from neutralization

Citation
M. Korenaga et al., A possible role of hypervariable region 1 quasispecies in escape of hepatitis C virus particles from neutralization, J VIRAL HEP, 8(5), 2001, pp. 331-340
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology
Journal title
JOURNAL OF VIRAL HEPATITIS
ISSN journal
1352-0504 → ACNP
Volume
8
Issue
5
Year of publication
2001
Pages
331 - 340
Database
ISI
SICI code
1352-0504(200109)8:5<331:APROHR>2.0.ZU;2-Q
Abstract
We examined serial changes in the hypervariable region 1(HVR1) quasispecies both in immune and nonimmune complexed hepatitis C virus (HCV) particles f rom 12 patients with chronic hepatitis C to elucidate the mechanism by whic h genetic diversification of HCV during the course of infection allows esca pe of virus from the humoural immune response. Immune and nonimmune complex es were separated by differential flotation centrifugation and immunoprecip itation, and their HVR1 quasispecies were determined by subcloning and sequ encing. The presence of a specific antibody against a specific viral clone in serum was examined in two patients by Western blotting of the correspond ing recombinant HVR1 protein. The distribution of HVR1 quasispecies in both immune and nonimmune complexes conspicuously changed over time in most of the patients studied. In seven patients, various HCV clones serially shifte d from nonimmune complexes to immune complexes. In four of them, a group of clones with similar HVR1 sequences to each other remained predominant in n onimmune complexes, whereas minor clones with sequences considerably diverg ent from the predominant clones shifted from, nonimmune complexes to immune complexes. These results suggest a mechanism for persistent infection of H CV, in which major HCV clones escape from neutralization by anti-HVR1 1 ant ibodies by generating considerably divergent minor 'decoy' clones which may be preferentially neutralized.