All three clones derived from the sample collected in 1999, during the first lamivudine treatment, showed two lamivudine resistant mutations (L526M and M550V), also detected in the major viral population by direct sequencing.
A major challenge is the extreme viral sequence variability among strains.
At week 156, the major CTL targets continued to be the two mutant epitopes, despite the consensus B epitope sequence being the major viral variant.
Viral sequence variability poses a major challenge, yet recent research has provided unprecedented views of the atomic structure of HCV epitopes and immune recognition by antibodies and T cell receptors.
Since very little genotype-3a viral sequence data were available for major parts of the polyprotein, we initially performed full-length viral sequence analysis in 20 treatment-naïve genotype-3a infected patients.
The isolation of substantial numbers of viral sequence variants at highly variable viral protein domains remains a major challenge.
Sequence analysis showed that a wild-type RVFV ZH501 preparation consisted of two major viral subpopulations, with a single nucleotide heterogeneity at nucleotide 847 of M segment (M847); one had a G residue at M847 encoding glycine in a major viral envelope Gn protein, while the other carried A residue encoding glutamic acid at the corresponding site.
Initially, the major viral population carried an isoleucine in position three of the epitope, 33ALIEICTEM41 (35I), while no subtype B consensus epitope sequences were found.
CD8+ T-cell responses drive viral sequence variations that may result in viral persistence by affecting the epitope processing and presentation or abrogating major histocompartibility complex (MHC) molecule binding, as well as T-cell receptor recognition.
In addition, several of these studies relied on population sequencing, a process that can result in biased estimates of viral diversity and recognition of only major viral genotype(s).
