De Luca, Andrea ORCID: 0000-0002-9561-9193, Di Giambenedetto, Simona, Lo Presti, Alessandra, Sierra, Saleta, Prosperi, Mattia, Cella, Eleonora ORCID: 0000-0002-7870-9744, Giovanetti, Marta ORCID: 0000-0002-5849-7326, Torti, Carlo, Caudai, Cinzia, Vicenti, Ilaria, Saladini, Francesco ORCID: 0000-0002-9934-377X, Almi, Paolo, Grima, Pierfrancesco, Blanc, Pierluigi, Fabbiani, Massimiliano ORCID: 0000-0002-1343-812X, Rossetti, Barbara, Gagliardini, Roberta ORCID: 0000-0002-6351-2623, Kaiser, Rolf, Ciccozzi, Massimo and Zazzi, Maurizio ORCID: 0000-0002-0344-6281 (2015). Two Distinct Hepatitis C Virus Genotype 1a Clades Have Different Geographical Distribution and Association With Natural Resistance to NS3 Protease Inhibitors. Open Forum Infect. Dis., 2 (2). CARY: OXFORD UNIV PRESS INC. ISSN 2328-8957

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Abstract

Background. Hepatitis C virus (HCV) genotype 1 is the most prevalent worldwide. Subtype 1a, compared with 1b, shows lower response rates and higher propensity to select for drug resistance to NS3 and selected NS5A and nonnucleoside NS5B inhibitors. Two distinct clades of subtype 1a have been described. Methods. Using Bayesian methodology, we performed a time-scaled phylogeny reconstruction of clade separation and characterized the geographic distribution, phylodynamics, and association with natural resistance variants of NS3 sequences from 362 patients carrying subtype 1a HCV. Results. All sequences segregated in 2 clearly distinct clades. Clade I showed an earlier origin from the common ancestor compared with clade II. Clade I virus was more prevalent in non-European countries, represented mostly by United States, compared with European (75.7% vs 49.3%; P < .001). The prevalence of the natural NS3 variant Q80K, associated with resistance to the macrocyclic protease inhibitor simeprevir, was detected in 51.6% of clade I and 0% of clade II (P < .001); clade I showed a lower genetic barrier for Q80K, whereas no sign of selective pressure at any protease inhibitor resistance-associated codon was detected. Conclusions. Hepatitis C virus subtype 1a clades have a clearly different distribution in Europe and the United States, and the natural resistance mutation Q80K is exclusively associated with clade I.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
De Luca, AndreaUNSPECIFIEDorcid.org/0000-0002-9561-9193UNSPECIFIED
Di Giambenedetto, SimonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lo Presti, AlessandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sierra, SaletaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prosperi, MattiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cella, EleonoraUNSPECIFIEDorcid.org/0000-0002-7870-9744UNSPECIFIED
Giovanetti, MartaUNSPECIFIEDorcid.org/0000-0002-5849-7326UNSPECIFIED
Torti, CarloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caudai, CinziaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vicenti, IlariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saladini, FrancescoUNSPECIFIEDorcid.org/0000-0002-9934-377XUNSPECIFIED
Almi, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grima, PierfrancescoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanc, PierluigiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fabbiani, MassimilianoUNSPECIFIEDorcid.org/0000-0002-1343-812XUNSPECIFIED
Rossetti, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gagliardini, RobertaUNSPECIFIEDorcid.org/0000-0002-6351-2623UNSPECIFIED
Kaiser, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ciccozzi, MassimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zazzi, MaurizioUNSPECIFIEDorcid.org/0000-0002-0344-6281UNSPECIFIED
URN: urn:nbn:de:hbz:38-411910
DOI: 10.1093/ofid/ofv043
Journal or Publication Title: Open Forum Infect. Dis.
Volume: 2
Number: 2
Date: 2015
Publisher: OXFORD UNIV PRESS INC
Place of Publication: CARY
ISSN: 2328-8957
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TREATMENT-NAIVE PATIENTS; PEGYLATED INTERFERON; HCV INFECTION; SUBSTITUTION RATES; GENETIC DIVERSITY; DRUG-RESISTANCE; BI 207127; ALPHA 2A; SIMEPREVIR; RIBAVIRINMultiple languages
Immunology; Infectious Diseases; MicrobiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41191

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