Decreased diversity of hepatitis C virus quasispecies during bone marrow transplantation

To elucidate the role of host immune status in the evolution and complexity of hepatitis C virus (HCV) quasispecies, three chronic HCV- infected patients who underwent bone marrow transplantation (BMT) were studied. The three transplanted patients' sera were sampled at pre-BMT, 3 months after BMT, and 12 months after BMT and the nucleotide diversity and substitution of the hypervariable region (HVR) of HCV quasispecies were analyzed. The nucleotide 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 first 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 was 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 on nucleotide substitution rate showed a higher value between pre- BMT and 3 months after 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 and increased accordingly. It was concluded that the evolution of HVR of HCV quasispecies related to the immune status of the host during BMT: after immunosuppression, an initial increase of viral populations was followed by the emergence of a dominant strain while the quasispecies gradually recovered as the immunity of the host gained its competence.