title: Analysis of Naturally Occurring Resistant Mutations to Hepatitis C Virus NS3 Protease Inhibitors: A Preliminary Study in South of Iran.
abstract: BACKGROUND
  Exploring the rate of naturally occurring NS3 protease mutants in HCV infected population is influential in the future therapeutic approaches.
  
  
  OBJECTIVE
  This study explored naturally occurring resistant mutations to protease inhibitors in a pilot study.
  
  
  METHODS
  We analyzed NS3 gene sequences in 7 HCV infected patients, referred to the central liver center, south of Iran. The protease domain was amplified by PCR followed by product extraction. Amplified NS3 genes were cloned by TA/cloning system. For each patient, clonal-sequencing was performed to improve mutation detection sensitivity. Then, the obtained sequences were compared with the reference sequences and final phylogenic tree was constructed. Afterwards, the sequences were studied to investigate point mutations.
  
  
  RESULTS
  Phylogenetic analysis between reference and amplified sequences demonstrated high similarity of all sequences with genotype 1. Interestingly, crucial protease resistant mutations were detected in V36 and R155 positions in one patient's sequence. Checking different clones of this patient confirmed V36L, as the dominant mutation while R155K was detected only in a few cases.
  
  
  CONCLUSIONS
  As revealed, naturally occurring resistant mutations, especially R155K in protease sequence were identified in 1 out of the 7 patients, so the rate of such mutations is estimated to be high. It seems that checking HCV patients before protease inhibitor treatment are necessary in the region.
authors.affiliation: Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors.forename: Mozhgan
authors.initials: M
authors.lastname: Afrasiabi
authors.affiliation: Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors.forename: Seyed Younes
authors.initials: SY
authors.lastname: Hosseini
authors.affiliation: Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Yaghobi
authors.affiliation: Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Fattahi
authors.affiliation: Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ardebili
authors.affiliation: Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Khodadad
keywords: Drug Resistance; Nonstructural Protein 3; Protease Inhibitors