Hepatitis C Viral Heterogeneity Based on Core Gene and an Attempt to Design Small Interfering RNA Against Strains Resistant to Interferon in Rawalpindi, Pakistan

How to Cite:Alavian SM. Hepatitis C Viral Heterogeneity Based on Core Gene and an Attempt to Design Small Interfering RNA Against Strains Resistant to Interferon in Rawalpindi, Pakistan. Hepat Mon. 2012;12(4):. doi: https://doi.org/10.5812/hepatmon.869

Abstract

Background: Global prevalence of Hepatitis C Virus (HCV) infection corresponds to about 130 million HCV positive patients worldwide. The only drug that effectively reduces viral load is interferon-α (IFN-α) and currently combination of IFN and ribavirin is the choice for treatment.
Objectives: The present study is aimed to resolve the genotypes based on core gene that might affect the response to interferon therapy. Furthermore an attempt was made to propose a powerful therapeutic approach by designing the siRNA from sequences of the same patients who remain resistant to IFN in this study.
Patients and Methods: To achieve the objectives, a sequence analysis was performed in five HCV ELISA positive subjects who have completed IFN treatment. Neighbor Joining (NJ) method was used to study the evolutionary relationship. Atomic models were predicted using online software PROCHECK and i- TASSER.
Results: Two new genotypes were reported for the first time namely 4a from suburban region of Rawalpindi and 6e from all over the Pakistan. According to Ramachandran plot, satisfactory atomic model was considered useful for further studies, i.e. to calculate HCV genotypes conservation at structural level, to find out critical binding sites for drug
designing, or to silence those binding sites by using appropriate siRNA. Single siRNA can be used to inhibit HCV RNA synthesis against genotype 3 and 4, as the predicted siRNA were originated from the same domain in studied HCV core region in both genotypes.
Conclusions: We can conclude that any change or mutation in core region might be the cause of HCV strains to resist against IFN therapy. Therefore, further understanding of the complex mechanism involved in disrupting viral response to therapy would facilitate the development of more effective therapeutic regimens. Additionally, a single designed siRNA can be used as an alternative for current therapy against more than one resistant HCV genotypes.

Implication for health policy/practice/research/medical education:
This study investigates the role of genetic heterogenity of hepatitis C virus in IFn resistance and detected 2 new genotypes 4a and 6e in Pakistani population. Besides this an alternative therapeutic tool siRNA is presented to be used against HCV instead of IFn. This research work will be informative and useful for those who are involved in medical prevention and therapy to chronic hepatitis C.
Please cite this paper as:
Kanwal S, Mahmood T. Hepatitis C Viral Heterogeneity Based on Core Gene and an Attempt to Design Small Interfering RNA Against Strains Resistant to Interferon in Rawalpindi, Pakistan. Hepat Mon. 2012;12(6): 398-407. DoI: 10.5812/hepatmon.6184

Keywords

Interferons

Small interfering RNA (siRNA)

Hepatitis C

Fulltext

Full text is available in PDF

Hepatitis C Viral Heterogeneity Based on Core Gene and an Attempt to Design Small Interfering RNA Against Strains Resistant to Interferon in Rawalpindi, Pakistan

Sobia Kanwal,

Tariq Mahmood

Kanwal S, Mahmood T. Hepatitis C Viral Heterogeneity Based on Core Gene and an Attempt to Design Small Interfering RNA Against Strains Resistant to Interferon in Rawalpindi, Pakistan. Hepat Mon. 2012;12(6):. doi: https://doi.org/10.5812/hepatmon.6184

9

Mar

2014

The IFN-λ Genetic Polymorphism Association With the Viral Clearance Induced by Hepatitis C Virus Treatment in Pakistani Patients

Imran Tipu,

Fiona Marriage,

Zia-ur-Rahman Farooqi,

Hazel Platt,

Muhammad Amin Athar,

Philip John Day

,et al.

Tipu I, Marriage F, Farooqi Z, Platt H, Athar MA, et al. The IFN-λ Genetic Polymorphism Association With the Viral Clearance Induced by Hepatitis C Virus Treatment in Pakistani Patients. Hepat Mon. 2014;14(3):e15076. doi: https://doi.org/10.5812/hepatmon.15076

9

May

2013

Sequence and Structural Analysis of 3' Untranslated Region of Hepatitis C Virus, Genotype 3a, From Pakistani Isolates

Sadia Anjum,

Sidra Ali,

Tahir Ahmad,

Muhammad Sohail Afzal,

Yasir Waheed,

Talha Shafi

,et al.

Anjum S, Ali S, Ahmad T, Afzal MS, Waheed Y, et al. Sequence and Structural Analysis of 3' Untranslated Region of Hepatitis C Virus, Genotype 3a, From Pakistani Isolates. Hepat Mon. 2013;13(5):e8390. doi: https://doi.org/10.5812/hepatmon.8390

23

Jun

2015

Phylogenetic and 2D/3D Analysis of HCV 1a NS4A Gene/Protein in Pakistani Isolates

Abrar Hussain,

Muhammad Idrees,

Muhammad Asif,

Liaqat Ali,

Mahmood Rasool

Hussain A, Idrees M, Asif M, Ali L, Rasool M. Phylogenetic and 2D/3D Analysis of HCV 1a NS4A Gene/Protein in Pakistani Isolates. Hepat Mon. 2015;15(6):e19936. doi: https://doi.org/10.5812/hepatmon.15(6)2015.19936

21

Jul

2020

Sofosbuvir and Ribavirin Combination Therapy Response in Various Hepatitis C Virus Genotypes in Peshawar, Khyber Pakhtunkhwa

Saima Ali Haider,

Bashir Ahmad,

Sajid Ali,

Ali Haider,

Shumaila Bashir,

Nourin Mahmood

Haider SA, Ahmad B, Ali S, Haider A, Bashir S, et al. Sofosbuvir and Ribavirin Combination Therapy Response in Various Hepatitis C Virus Genotypes in Peshawar, Khyber Pakhtunkhwa. Jundishapur J Microbiol. 2020;13(6):e99625. doi: https://doi.org/10.5812/jjm.99625

Import into EndNote Import into BibTex

Crossmark

Checking

Share on

Comments

Number of Comments:0

Cited by

Scopus by DOI: 7
Last Update: 1 week ago
Scopus by Title: 2
Last Update: 1 week ago
Scopus by Title (Ref): 0
Last Update: 1 week ago
CrossRef: 3
Last Update: 3 days ago

Metrics

Licensing and reuse information

Ordering Reprints

Articles are published under the Creative Commons license stated on each article. No permission or royalty fee is required for uses permitted by that license. CCC handles optional bulk and customized reprint orders. Any quotation covers production and delivery services only, not copyright permission. > Request Reprints from CCC

Search Relations

Author(s):

Seyed Moayed Alavian:[PubMed][Scholar]

Official Journal of Research Center for Gastroenterology and Liver Diseases

Outlines

Hepatitis C Viral Heterogeneity Based on Core Gene and an Attempt to Design Small Interfering RNA Against Strains Resistant to Interferon in Rawalpindi, Pakistan

Abstract

Fulltext

Similar Articles

Hepatitis C Viral Heterogeneity Based on Core Gene and an Attempt to Design Small Interfering RNA Against Strains Resistant to Interferon in Rawalpindi, Pakistan

The IFN-λ Genetic Polymorphism Association With the Viral Clearance Induced by Hepatitis C Virus Treatment in Pakistani Patients

Sequence and Structural Analysis of 3' Untranslated Region of Hepatitis C Virus, Genotype 3a, From Pakistani Isolates

Phylogenetic and 2D/3D Analysis of HCV 1a NS4A Gene/Protein in Pakistani Isolates

Sofosbuvir and Ribavirin Combination Therapy Response in Various Hepatitis C Virus Genotypes in Peshawar, Khyber Pakhtunkhwa

Crossmark

Checking

Last Update: 1 week ago

Last Update: 1 week ago

Last Update: 1 week ago

Last Update: 3 days ago