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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 107, No. 2, 2012, pp. 254-261
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Bioline Code: oc12037
Full paper language: English
Document type: Research Article
Document available free of charge
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Memórias do Instituto Oswaldo Cruz, Vol. 107, No. 2, 2012, pp. 254-261
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Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs
Peres-da-Silva, Allan; de Almeida, Adilson José & Lampe, Elisabeth
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.
Keywords
genetic diversity - NS3 protease - hepatitis C virus - direct-acting antiviral agents
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