title: Molecular characterization of hepatitis C virus core region in moroccan intravenous drug users.
abstract: Intravenous drug users (IDUs) represent a highly-infected reservoir for Hepatitis C virus (HCV) worldwide, harboring some of the most elevated prevalences and majority of the epidemic in developed nations. Studies aimed at sequencing regions of the viral genome uncovered amino acid mutations, some of which have been implicated in resistance to standard of care pegylated interferon/Ribavirin double therapy. Using the nested PCR method on the Core region of HCV strains in Moroccan IDUs living in the Tangier region this study sought to identify genotype-specific amino acid mutations, followed by Phylogenetic methods in order to compare them with international strains so as to identify sequences of highest homology. Genotyping was confirmed and recombination events excluded by line-probe assay. Italy was found most homologous for genotypes 1a and 3a, Iran for genotype 1a and Egypt for genotype 4a. Amino Acid Mutation analysis revealed the following novel genotype 3a-specific mutations: N16I, L36V, T49A, P71S, T75S, and T110N. The outcome of this work describes the HCV genetic heterogeneity in high-risk intravenous drug users, and it gives clues to the global migratory flow of genotypes as they cross geographical boundaries between various IDU populations and identifies "signature" amino acid mutations traceable to HCV genotype 3a. Identification of key amino acid positions in the HCV Core region with higher rates of mutations paves the way for eventual clinical trials seeking to establish a link between these recurrent mutations and response to standard of care Interferon and Ribavirin antiviral therapy. J. Med. Virol. 88:1376-1383, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Molecular Biology Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Roxana-Delia
authors.initials: RD
authors.lastname: Trimbitas
authors.affiliation: Virology Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Naouar
authors.initials: N
authors.lastname: Fayssel
authors.affiliation: Hasnouna Center of Addictology, Tangier, Morocco.
authors.forename: Fatima-Zahra
authors.initials: FZ
authors.lastname: Serghini
authors.affiliation: Virology Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Lahcen
authors.initials: L
authors.lastname: Wakrim
authors.affiliation: Oncovirology Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Meriem
authors.initials: M
authors.lastname: Khyatti
authors.affiliation: Hasnouna Center of Addictology, Tangier, Morocco.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Essalhi
authors.affiliation: Delegation of Public Health, Ministry of Health, Tetouan Public Hospital, Tetouan, Morocco.
authors.forename: Abdelkrim Meziane
authors.initials: AM
authors.lastname: Bellefquih
authors.affiliation: Molecular Biology Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco.
authors.forename: Abdelouaheb
authors.initials: A
authors.lastname: Benani
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use; D004197:Disease Reservoirs; D055030:Drug Users; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009018:Morocco / Q000453:epidemiology; D009154:Mutation; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D015819:Substance Abuse, Intravenous / Q000150:complications* / Q000453:epidemiology; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D014758:Viral Core Proteins; D012254:Ribavirin; D007372:Interferons
keywords: HCV core region; Morocco; amino acid mutations; hepatitis C virus; intravenous drug user; phylogenetic analysis