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Study of PKRBD in HCV genotype 3a infected patients in response to interferon therapy in Pakistani population

Atika Mansoor1*, Lubna Ali1, Noor-ul Sabah1, Asraf Hussain Hashmi1, Mohammad Haroon Khan2, Syed Ali Raza Kazmi1, Nafees Ahmad1, Saima Siddiqi1 and Khalid Mehmood Khan3

Author Affiliations

1 Institute of Biomedical and Genetic Engineering, 24-Mauve area, G-9/1, Islamabad 44000, Pakistan

2 Department of Bioinformatics, Muhammad Ali Jinnah University, Islamabad, Pakistan

3 Pakistan Academy of Sciences, Islamabad, Pakistan

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Virology Journal 2013, 10:352  doi:10.1186/1743-422X-10-352

Published: 9 December 2013



Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma and infects about 3% world population. Response to interferon therapy depends upon the genotype of the virus and factors associated with the host. Despite a good response to interferon therapy, a considerable number of genotype 3a infected patients remains unalleviated.


In total forty-nine patients including twenty-five non-responders (non-SVR) and twenty-four responders (SVR) were recruited. Patients were tested for viral status at different intervals and the isolated RNA was sequenced for the NS5A region in both groups. The comparison of PKRBD of HCV between the SVR and non-SVR patients did not confirm any significant difference in the number of mutations. However, when the sequence downstream to the PKRBD of NS5A was compared, two important statistically significant mutations were observed; at positions 2309 (Ala to Ser) and 2326 (Gly to Ala). These mutations were then analysed for tertiary protein structure and important structural changes were observed. Statistically significant difference was also observed when age groups of patients were compared; younger patients showed better response than the older ones.


The region between PKRBD and IRRDR may be important for prediction of response to IFN therapy for genotype 3a. ISDR and PKRBD have not shown any involvement in treatment response. Further functional analyses of these findings can help in understanding the involvement of the NS5A region in interferon treatment of HCV-3a infected patients.