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

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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 (n = 61), PKR binding domain (n = 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 (P = 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.

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Authors and Affiliations

  1. Department of Gastroenterology, G.B. Pant Hospital, University of Delhi, New Delhi, India

    Ankur Goyal, Syed S. Hissar & Shiv K. Sarin

  2. Institute of Genomic and Integrative Biology, Mall Road, Delhi, India

    Ankur Goyal & Naveen Arora

  3. Dr. Ambedkar Center for Biomedical Research, University of Delhi, New Delhi, India

    Ankur Goyal

  4. Internal Medicine II, Saarland University Hospital, Homburg/Saar, Germany

    Wolf P. Hofmann, Eva Hermann, Stella Traver, Stefan Zeuzem & Christoph Sarrazin

  5. Department of Medicine II, University of Freiburg, Freiburg, Germany

    Hubert E. Blum

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  1. Ankur Goyal
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  2. Wolf P. Hofmann
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  3. Eva Hermann
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  4. Stella Traver
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Correspondence to Shiv K. Sarin.

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Ankur Goyal and Wolf P. Hofmann contributed equally to this work.

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Goyal, A., Hofmann, W.P., Hermann, E. et al. The hepatitis C virus NS5A protein and response to interferon α: mutational analyses in patients with chronic HCV genotype 3a infection from India. Med Microbiol Immunol 196, 11–21 (2007). https://doi.org/10.1007/s00430-006-0024-z

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