Medical Microbiology and Immunology

, Volume 196, Issue 1, pp 11–21 | Cite as

The hepatitis C virus NS5A protein and response to interferon α: mutational analyses in patients with chronic HCV genotype 3a infection from India

  • Ankur Goyal
  • Wolf P. Hofmann
  • Eva Hermann
  • Stella Traver
  • Syed S. Hissar
  • Naveen Arora
  • Hubert E. Blum
  • Stefan Zeuzem
  • Christoph Sarrazin
  • Shiv K. Sarin
Original Investigation

Abstract

The hepatitis C virus (HCV) non-structural (NS)5A protein is linked to interferon α resistance in vitro and higher numbers of NS5A amino acid (aa) variations in HCV 1a/b isolates are associated with virologic response to interferon α-based therapy in vivo. Here, we aimed to study NS5A aa variations in Indian patients undergoing interferon α/ribavirin treatment infected with HCV 3a. The NS5A region [aa 2194–2401, comprising interferon sensitivity determining region, protein kinase resource (PKR) binding domain, V3 region] was sequenced from pre-treatment sera of 24 patients with HCV 3a infection. Mean number and physicochemical properties of aa variations (conserved vs. non-conserved) were assessed. Additionally, published NS5A sequences [NS5A region (= 61), PKR binding domain (= 111)] of characterized HCV 3a isolates were analyzed. The mean number of NS5A aa variations was not correlated with treatment response in our cohort. When all available NS5A sequences were included, a higher number of non-conserved aa variations within PKR binding domain and an extended V3 region of NS5A was associated with virologic response (= 0.004 and 0.05, respectively). Mutational analyses of a large number of NS5A sequences suggest, that a higher number of non-conserved aa variations within the PKR binding domain and the extended V3 region is correlated with virologic response in HCV 3a infected patients.

Keywords

HCV NS5A aa Variations Interferon α ISDR 

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Ankur Goyal
    • 1
    • 2
    • 3
  • Wolf P. Hofmann
    • 4
  • Eva Hermann
    • 4
  • Stella Traver
    • 4
  • Syed S. Hissar
    • 1
  • Naveen Arora
    • 2
  • Hubert E. Blum
    • 5
  • Stefan Zeuzem
    • 4
  • Christoph Sarrazin
    • 4
  • Shiv K. Sarin
    • 1
  1. 1.Department of GastroenterologyG.B. Pant Hospital, University of DelhiNew DelhiIndia
  2. 2.Institute of Genomic and Integrative BiologyDelhiIndia
  3. 3.Dr. Ambedkar Center for Biomedical ResearchUniversity of DelhiNew DelhiIndia
  4. 4.Internal Medicine IISaarland University HospitalHomburg/SaarGermany
  5. 5.Department of Medicine IIUniversity of FreiburgFreiburgGermany

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