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A newly discovered hepatitis C virus (HCV) genotype 1b subtype harbors multiple resistance-associated mutations that combine to block therapeutic effect of NS5A inhibitor direct-acting antivirals (DAAs).
Josep Quer, PhD, Liver Disease Laboratory-Viral Hepatitis, Vall d’Hebron Institut Recerca-Hospital Universitari, Barcelona and colleagues report the identification of a new HCV genotype 1 subtype isolated from a treatment-naive patient in Equatorial Guinea.
“This novel isolate was identified during routine classification of the HCV virus in patient samples using a high-resolution HCV subtyping method,” Quer and colleagues wrote. “Phylogenetic analysis, genetic distance analysis, and sliding window analysis of this genome (GenBank KY348757) clearly demonstrated that our isolate is not a recombinant product of different subtypes and that the genetic distance to the closest accepted reference sequence is higher than 15%.”
The HCV isolate is not only unique as a new subtype of genotype 1, but for harboring multiple resistance-associated substitutions (RASs), without apparent exposure to treatment agents which can prompt their manifestation.
Quer and colleagues point out that in subtype 1b, a single L31V or a Y93H substitution emerging in the viral genome has been shown to increase resistance to daclatasvir (Daklinza) by 15-fold and 12-fold, respectively. A virus with both mutations becomes 5425 times more resistant, according to the investigators.
“The most interesting observation from our isolate is that the virus is a natural carrier of L31V and Y93H substitutions in the same genome, as well as H/P58S and E62Q, which have been associated with varying levels of resistance to DAA-based treatments in other subtypes,” Quer and colleagues noted. “Hence this subtype may be resistant to NS5A inhibitor drugs.”
The report, “New hepatitis C virus genotype 1 subtype naturally harbouring resistance-associated mutations to NS5A inhibitors,” was published in the January issue of the Journal of General Virology.
Read complete news article here: http://www.mdmag.com/medical-news/newly-discovered-hcv-subtype-is-resistant-to-antiviral-treatment