title: Study of PKRBD in HCV genotype 3a infected patients in response to interferon therapy in Pakistani population.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Biomedical and Genetic Engineering, 24-Mauve area, G-9/1, Islamabad 44000, Pakistan. atikamansoor@hotmail.com.
authors: Atika
authors: A
authors: Mansoor
authors: Lubna
authors: L
authors: Ali
authors: Noor-ul
authors: NU
authors: Sabah
authors: Asraf Hussain
authors: AH
authors: Hashmi
authors: Mohammad Haroon
authors: MH
authors: Khan
authors: Syed Ali Raza
authors: SA
authors: Kazmi
authors: Nafees
authors: N
authors: Ahmad
authors: Saima
authors: S
authors: Siddiqi
authors: Khalid Mehmood
authors: KM
authors: Khan
mesh_terms: D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008875:Middle Aged; D010154:Pakistan; D054730:Protein Interaction Domains and Motifs; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D055815:Young Adult; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase