A particular hepatitis C virus protease NS3 gene pattern in a patient not responding to interferon-ribavirin therapy

Excerpt

Hepatitis C virus (HCV) is characterized by a high degree of genetic heterogeneity. This is a consequence of its rapid turnover in vivo and of the low fidelity of its RNA-dependent RNA polymerase, which lacks proofreading activity. Its high propensity to mutate is also reflected by the existence of closely related genomes, known as quasispecies [1]. NS3 protease is essential for HCV replication. It acts via a catalytic triad consisting of a histidine, an aspartate and a serine. It is also one of the most promising targets for specific anti-HCV therapy [2]. Although the NS3 protease is considered to be one of the least variable genes in the HCV genome, we previously found an appreciable polymorphism in this genomic region in 294 HCV genotype 1 clones isolated from the serum of 17 infected patients [3]. Reported here is a particular pattern, including three deletions and one insertion, found in four clones among 19 NS3 protease variants of a quasispecies detected in one of these patients. …