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
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.