To elucidate the role of host immune status in the evolution and complexity
of hepatitis C virus (HCV) quasispecies, three chronic HCV-infected patien
ts who underwent bone marrow transplantation (BMT) were studied. The three
transplanted patients' sera were sampled at pre-BMT, 3 months after BMT, an
d 12 months after BMT and the nucleotide diversity and substitution of the
hypervariable region (HVR) of HCV quasispecies; were analyzed. The nucleoti
de diversity was high at the pre-BMT period (28.2-43.4 x 10(-2) nucleotide
difference/site). HVR of HCV quasispecies then became homogeneous in the fi
rst 3 months after BMT (0.11-6.40 x 10(-2) nucleotide difference/site). The
nucleotide diversity of HVR at 12 months after BMT of all three patients w
as higher than that of 3 months after BMT but still lower than that of pre-
BMT (2.09-6.40 x 10(-2) nucleotide difference/site). The analysis nucleotid
e substitution rate showed a higher value between pre-BMT and 3 months afte
r BMT (0.624-0.708 nucleotide difference/site per year) than that between 3
months and 12 months after BMT (0.072-0.127 nucleotide difference/site per
year). HCV RNA titer decreased when the host had a low white cell count an
d increased accordingly. It was concluded that the evolution of HVR of HCV
quasispecies related to the immune status of the host during BMT: after imm
unosuppression, an initial increase of viral populations was followed by th
e emergence of a dominant strain while the quasispecies gradually recovered
as the immunity of the host gained its competence. J. Med. Virol, 58:132-1
38, 1999. (C) 1999 Wiley-Liss, Inc.