Universität zu Köln

Knops, Elena, Sierra, Saleta, Kalaghatgi, Prabhav, Heger, Eva, Kaiser, Rolf and Kalinina, Olga, V (2018). Epistatic Interactions in NS5A of Hepatitis C Virus Suggest Drug Resistance Mechanisms. Genes, 9 (7). BASEL: MDPI. ISSN 2073-4425

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Abstract

Hepatitis C virus (HCV) causes a major health burden and can be effectively treated by direct-acting antivirals (DAAs). The non-structural protein 5A (NS5A), which plays a role in the viral genome replication, is one of the DAAs' targets. Resistance-associated viruses (RAVs) harbouring NS5A resistance-associated mutations (RAMs) have been described at baseline and after therapy failure. A mutation from glutamine to arginine at position 30 (Q30R) is a characteristic RAM for the HCV sub/genotype (GT) 1a, but arginine corresponds to the wild type in the GT-1b; still, GT-1b strains are susceptible to NS5A-inhibitors. In this study, we show that GT-1b strains with R30Q often display other specific NS5A substitutions, particularly in positions 24 and 34. We demonstrate that in GT-1b secondary substitutions usually happen after initial R30Q development in the phylogeny, and that the chemical properties of the corresponding amino acids serve to restore the positive charge in this region, acting as compensatory mutations. These findings may have implications for RAVs treatment.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knops, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED Sierra, Saleta UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalaghatgi, Prabhav UNSPECIFIED UNSPECIFIED UNSPECIFIED Heger, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaiser, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalinina, Olga, V UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-180986
DOI:	10.3390/genes9070343
Journal or Publication Title:	Genes
Volume:	9
Number:	7
Date:	2018
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4425
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOTYPE 1 INFECTION; COMPENSATORY MUTATIONS; PLUS RIBAVIRIN; PARITAPREVIR-RITONAVIR; COMBINATION THERAPY; NATURAL PREVALENCE; CRYSTAL-STRUCTURE; HCV; VARIANTS; DOMAIN Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18098