Abstract
The hepatitis C virus (HCV) NS3 protease has been one of the molecular targets of new therapeutic approaches. Its genomic sequence variability in Brazilian HCV isolates is poorly documented. To obtain more information on the magnitude of its genetic diversity, 114 Brazilian HCV samples were sequenced and analysed together with global reference sequences. Genetic distance (d) analyses revealed that subtype 1b had a higher degree of heterogeneity (d = 0.098) than subtypes 1a (d = 0.060) and 3a (d = 0.062). Brazilian isolates of subtype 1b were distributed in the phylogenetic tree among sequences from other countries, whereas most subtype 1a and 3a sequences clustered into a single branch. Additional characterisation of subtype 1a in clades 1 and 2 revealed that all but two Brazilian subtype 1a sequences formed a distinct and strongly supported (approximate likelihood-ratio test = 93) group of sequences inside clade 1. Moreover, this subcluster inside clade 1 presented an unusual phenotypic characteristic in relation to the presence of resistance mutations for macrocyclic inhibitors. In particular, the mutation Q80K was found in the majority of clade 1 sequences, but not in the Brazilian isolates. These data demonstrate that Brazilian HCV subtypes display a distinct pattern of genetic diversity and reinforce the importance of sequence information in future therapeutic approaches.
Highlights
The hepatitis C virus (HCV) has a worldwide distribution, with an estimated 130 million people being infected (Alter 2007)
The entire NS3 protease domain of the HCV genome was analysed among 114 patients infected with HCV subtypes 1a (n = 48; 42%), 1b (n = 53; 46%) or 3a (n = 13; 11%)
There is little information on the extent of the natural genetic variability of the HCV NS3 protease region from different viral subtypes isolated in Latin America
Summary
Fig. 3: maximum-likelihood phylogenetic tree of hepatitis C virus subtype 3a from NS3 protease sequences showing evolutionary relationships between 13 Brazilian (red branches) and representative sequences from Europe (blue branches) (n = 77) and North America (green branches) (n = 12). Fig. 4: maximum-likelihood phylogenetic tree of hepatitis C virus (HCV) subtype 1a sequences for clade characterization estimated from NS3 protease sequences showing evolutionary relationships between 48 Brazilian (red circles) HCV subtype 1a strains and 120 representative subtype 1a sequences of clade 1 (green circles) and clade 2 (blue triangles). Both clades are formed by isolates from Europe and North America.
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