title: Characterization of hepatitis C Virus genotype 3a hypervariable region 1 in patients achieved rapid virological response to alpha interferon and ribavirin combination therapy.
abstract: BACKGROUND
  Hepatitis C virus roots a chronic liver disease. Currently approved treatment strategy includes administration of alpha interferon and ribavirin combined therapy for 24-48 weeks. One of the predictor of sustained virological response is an early virological response to treatment characterized as rapid response. Hyper variable region 1 (HVR1) of E2 protein is responsible for viral entry and acts as a target for neutralizing antibodies. Any mutation in this region would effect virus interaction with target cell and viral persistence.
  
  
  METHODS
  Thirty one clones of six pre-treatment samples subjected to combination therapy were investigated. Three of the patients were rapid responders (R1, R2 and R3) and two were breakthrough responders (BT1 and BT2). Envelope 2 gene was amplified, cloned and sequenced. Amino acid substitution, frequency, composition and antigenic properties of HVR 1 of E2 protein were studied.
  
  
  RESULTS
  In both rapid responders (R.R) (14 amino acid sites) and breakthrough responders (BT.R) (13 amino acid sites) half of the amino acid sites were either conserved or resistant to any physiochemical change due to amino acid substitution. It also indicated that average composition of hydrophilic and basic amino acids were comparatively lower in rapid responders than other samples affecting probable interaction of virus with target cells. A central non antigenic region was constant among the breakthrough responders but differed in length significantly among rapid responders reflecting the adaptive nature of HVR1 to the immune response.
  
  
  CONCLUSIONS
  We observed that although HVR1is quite variable region in HCV 3a patients responding differently to treatment it still maintains its physiochemical properties for its proper functioning and viability.
authors: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors: Madiha
authors: M
authors: Akram
authors: Muhammad
authors: M
authors: Idrees
authors: Abrar
authors: A
authors: Hussain
authors: Samia
authors: S
authors: Afzal
authors: Muhammad
authors: M
authors: Ilyas
authors: Shamail
authors: S
authors: Zafar
authors: Mahwish
authors: M
authors: Aftab
authors: Sadaf
authors: S
authors: Badar
authors: Bushra
authors: B
authors: Khubaib
references: Hepatology. 1995 Oct;22(4 Pt 1):1050-6
references: 7557850
references: J Viral Hepat. 2000 Jan;7(1):36-42
references: 10718941
references: Hepatology. 2002 Nov;36(5 Suppl 1):S21-9
references: 12407573
references: Trop Gastroenterol. 2008 Oct-Dec;29(4):194-201
references: 19323087
references: J Virol. 2003 Feb;77(3):1856-67
references: 12525620
references: Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3392-6
references: 1849654
references: Eur J Public Health. 2011 Oct;21(5):638-42
references: 20601693
references: Cell Microbiol. 2008 Apr;10(4):821-7
references: 18081727
references: J Clin Microbiol. 2003 Aug;41(8):3615-22
references: 12904364
references: EMBO J. 1998 Jul 1;17(13):3521-33
references: 9649423
references: N Engl J Med. 1997 Jan 30;336(5):347-56
references: 9011789
references: BMC Gastroenterol. 2009 Jan 20;9:5
references: 19152711
references: Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12766-71
references: 10535997
references: Hepatology. 2002 Nov;36(5 Suppl 1):S47-56
references: 12407576
references: World J Gastroenterol. 2009 Dec 7;15(45):5647-53
references: 19960560
references: J Viral Hepat. 1999 Jul;6 Suppl 1:41-6
references: 10760034
references: J Dig Dis. 2008 May;9(2):95-103
references: 18419643
references: Hepatology. 1999 Mar;29(3):897-903
references: 10051495
references: Virology. 1991 Feb;180(2):842-8
references: 1846505
references: J Virol. 2000 Jan;74(2):661-8
references: 10623727
references: Nat Med. 1997 Aug;3(8):866-71
references: 9256277
references: Mol Biol Evol. 2007 Aug;24(8):1596-9
references: 17488738
references: J Virol. 2001 Jun;75(12):5703-10
references: 11356980
references: Biochemistry. 1986 Sep 23;25(19):5425-32
references: 2430611
references: Hepatology. 2002 Nov;36(5 Suppl 1):S35-46
references: 12407575
references: J Gen Virol. 2004 Jan;85(Pt 1):39-46
references: 14718618
references: Vaccine. 2002 Aug 19;20(25-26):3095-103
references: 12163260
references: J Virol. 1998 Jun;72(6):4893-905
references: 9573256
references: Hepatology. 2002 Nov;36(5 Suppl 1):S245-52
references: 12407600