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Article

Mutations in the STAT1‑interacting domain of the hepatitis C virus core protein modulate the response to antiviral therapy

  • Authors:
    • Sadia Anjum
    • Muhammad Sohail Afzal
    • Tahir Ahmad
    • Baber Aslam
    • Yasir Waheed
    • Talha Shafi
    • Ishtiaq Qadri
  • View Affiliations / Copyright

    Affiliations: Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan
  • Pages: 487-492
    |
    Published online on: June 25, 2013
       https://doi.org/10.3892/mmr.2013.1541
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Abstract

RNA viruses, such as hepatitis C virus (HCV), have markedly error-prone replication, resulting in high rates of mutagenesis. In addition, the standard treatment includes ribavirin, a base analog that is likely to cause mutations in different regions of the HCV genome, resulting in deleterious effects on HCV itself. The N-terminal region of the core protein is reported to block interferon (IFN) signaling by interaction with the STAT1‑SH2 domain, resulting in HCV resistance to IFN therapy. In this study, mutations in the HCV core protein from IFN/ribavirin‑treated patients were analyzed, with particular focus on the N‑terminal domain of the HCV core which is reported to interact with STAT1. HCV PCR positive patients enrolled in this study were either undergoing pegylated IFN/ribavirin bitherapy and had completed 12 weeks of initial treatment or were treatment‑naïve patients. The HCV core protein was cloned and sequenced from these patients and mutations observed in the STAT1‑interacting domain of the core protein from treated patients were characterized using in silico interaction to depict the role of these mutations in disease outcomes. Our results suggest that the amino acids at positions 2, 3, 8, 16 and 23 of the HCV core protein are critical for core-STAT1 interaction and ribavirin-induced mutations at these positions interfere with the interaction, resulting in a better response of the treated patients. In conclusion, this study anticipates that HCV core residues 2, 3, 8, 16 and 23 directly interact with STAT1. We propose that IFN/ribavirin bitherapy‑induced mutations in the STAT1‑interacting domain of the HCV core protein may be responsible for the improved therapeutic response and viral clearance, thus amino acids 1-23 of the N-terminus of the core protein are an ideal antiviral target. However, this treatment may give rise to resistant variants that are able to escape the current therapy. We propose similar studies in responsive and non-responsive genotypes in order to gain a broader picture of this proposed mechanism of viral clearance.
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Copy and paste a formatted citation
Spandidos Publications style
Anjum S, Afzal MS, Ahmad T, Aslam B, Waheed Y, Shafi T and Qadri I: Mutations in the STAT1‑interacting domain of the hepatitis C virus core protein modulate the response to antiviral therapy. Mol Med Rep 8: 487-492, 2013.
APA
Anjum, S., Afzal, M.S., Ahmad, T., Aslam, B., Waheed, Y., Shafi, T., & Qadri, I. (2013). Mutations in the STAT1‑interacting domain of the hepatitis C virus core protein modulate the response to antiviral therapy. Molecular Medicine Reports, 8, 487-492. https://doi.org/10.3892/mmr.2013.1541
MLA
Anjum, S., Afzal, M. S., Ahmad, T., Aslam, B., Waheed, Y., Shafi, T., Qadri, I."Mutations in the STAT1‑interacting domain of the hepatitis C virus core protein modulate the response to antiviral therapy". Molecular Medicine Reports 8.2 (2013): 487-492.
Chicago
Anjum, S., Afzal, M. S., Ahmad, T., Aslam, B., Waheed, Y., Shafi, T., Qadri, I."Mutations in the STAT1‑interacting domain of the hepatitis C virus core protein modulate the response to antiviral therapy". Molecular Medicine Reports 8, no. 2 (2013): 487-492. https://doi.org/10.3892/mmr.2013.1541
Copy and paste a formatted citation
x
Spandidos Publications style
Anjum S, Afzal MS, Ahmad T, Aslam B, Waheed Y, Shafi T and Qadri I: Mutations in the STAT1‑interacting domain of the hepatitis C virus core protein modulate the response to antiviral therapy. Mol Med Rep 8: 487-492, 2013.
APA
Anjum, S., Afzal, M.S., Ahmad, T., Aslam, B., Waheed, Y., Shafi, T., & Qadri, I. (2013). Mutations in the STAT1‑interacting domain of the hepatitis C virus core protein modulate the response to antiviral therapy. Molecular Medicine Reports, 8, 487-492. https://doi.org/10.3892/mmr.2013.1541
MLA
Anjum, S., Afzal, M. S., Ahmad, T., Aslam, B., Waheed, Y., Shafi, T., Qadri, I."Mutations in the STAT1‑interacting domain of the hepatitis C virus core protein modulate the response to antiviral therapy". Molecular Medicine Reports 8.2 (2013): 487-492.
Chicago
Anjum, S., Afzal, M. S., Ahmad, T., Aslam, B., Waheed, Y., Shafi, T., Qadri, I."Mutations in the STAT1‑interacting domain of the hepatitis C virus core protein modulate the response to antiviral therapy". Molecular Medicine Reports 8, no. 2 (2013): 487-492. https://doi.org/10.3892/mmr.2013.1541
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