NS5AISDR-V3 region genetic variability of Tunisian HCV-1b strains: Correlation with the response to the combined interferon/ribavirin therapy

N. Bouzgarrou, E. Hassen, W. Mahfoudh, S. Gabbouj, E. Schvoerer, A. Ben Yahia, N. Ben Mami, H. Triki, Lotfi Chouchane

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

In the non-structural protein 5A (NS5A) of hepatitis C virus (HCV), mutations within the interferon sensitivity-determining region (ISDR), the PKR-binding domain (PKR-BD), the variable region 3 (V3), and the interferon/ribavirin resistance-determining region (IRRDR) have been correlated with the IFN-based therapy response. In Tunisia, where a high prevalence of HCV-1b has been found, no data regarding the implication of NS5A in treatment response were available. The current study examined the relationship between the pre-treatment mutation number within ISDR, PKR-BD, V3, IRRDR, as well as in the entire ISDR-V3 region of NS5A (aa 2209-2379) and the response to the 48-week course of combined IFN plus ribavirin therapy in 15 HCV-1b-infected Tunisian patients. Referring to HCV-J sequence, a significant high genetic variability was observed within PKR-BD in the sustained virological responder patients compared to non-responders (P = 0.040). More importantly, when considering the entire region from ISDR to V3, referred to as NS5AISDR-V3, a clear difference in the mutation number was observed between sustained virological responders (19.6 ± 3.16) and non-responders (15.0 ± 1.41) (P = 0.002). Additionally, a more detailed analysis of NS5AISDR-V3 region revealed an elevated degree of mutation rate within the region located between amino acids 2282 and 2308 (P = 0.0006). Interestingly, an analysis of specific amino acid variations defined proline and serine at position 2300 as signature patterns for sensitive and resistant strains, respectively. The genetic variability within the NS5A region of HCV-1b strains was associated with the response to the combined IFN plus ribavirin therapy in our Tunisian cohort.

Original languageEnglish
Pages (from-to)2021-2028
Number of pages8
JournalJournal of Medical Virology
Volume81
Issue number12
DOIs
Publication statusPublished - Dec 2009

Fingerprint

Ribavirin
Hepacivirus
Interferons
Mutation
Proteins
Therapeutics
Amino Acids
Tunisia
Mutation Rate
Proline
Serine

Keywords

  • Hepatitis C virus
  • NS5A
  • Treatment response
  • Tunisia

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

NS5AISDR-V3 region genetic variability of Tunisian HCV-1b strains : Correlation with the response to the combined interferon/ribavirin therapy. / Bouzgarrou, N.; Hassen, E.; Mahfoudh, W.; Gabbouj, S.; Schvoerer, E.; Ben Yahia, A.; Ben Mami, N.; Triki, H.; Chouchane, Lotfi.

In: Journal of Medical Virology, Vol. 81, No. 12, 12.2009, p. 2021-2028.

Research output: Contribution to journalArticle

Bouzgarrou, N, Hassen, E, Mahfoudh, W, Gabbouj, S, Schvoerer, E, Ben Yahia, A, Ben Mami, N, Triki, H & Chouchane, L 2009, 'NS5AISDR-V3 region genetic variability of Tunisian HCV-1b strains: Correlation with the response to the combined interferon/ribavirin therapy', Journal of Medical Virology, vol. 81, no. 12, pp. 2021-2028. https://doi.org/10.1002/jmv.21641
Bouzgarrou, N. ; Hassen, E. ; Mahfoudh, W. ; Gabbouj, S. ; Schvoerer, E. ; Ben Yahia, A. ; Ben Mami, N. ; Triki, H. ; Chouchane, Lotfi. / NS5AISDR-V3 region genetic variability of Tunisian HCV-1b strains : Correlation with the response to the combined interferon/ribavirin therapy. In: Journal of Medical Virology. 2009 ; Vol. 81, No. 12. pp. 2021-2028.
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