title: Analysis of hepatitis C virus quasispecies transmission and evolution in patients infected through blood transfusion.
abstract: OBJECTIVE
  Studies on hepatitis C virus (HCV) quasispecies dynamics in the natural course of infection are rare owing to difficulties in obtaining samples from the early phase of infection.
  
  
  METHODS
  We studied 15 patients from the Transfusion-Transmitted Viruses Study who seroconverted to anti-HCV after receiving infected blood. Follow-up serum samples were collected every 2-3 weeks for 6 months, at 10 months, and at 11-16 years. Viral quasispecies in the second envelope hypervariable region 1 (E2/HVR1) and 5' untranslated region (5'UTR) were analyzed with single-strand conformation polymorphism (SSCP) and heteroduplex mobility assay (HMA).
  
  
  RESULTS
  Seven patients cleared infection within 7-24 weeks (mean, 14.0 wk) and 3 patients eventually became anti-HCV negative. In 6 patients with resolving hepatitis the SSCP band pattern remained stable, whereas in one patient minor changes appeared before clearance. In contrast, in all 8 patients progressing to chronicity, major changes in the E2/HVR1 quasispecies developed at 8-22 weeks (mean, 13.1 wk). Shannon entropy and medium mobility shift values derived from HMA gels remained stable in patients with resolving hepatitis but changed in those who developed chronic infection. Only 2 patients showed minor changes in 5'UTR. A decrease in E2/HVR1 complexity at the time of transmission (bottleneck) was found in 5 patients altogether.
  
  
  CONCLUSIONS
  Changes in E2/HVR1 quasispecies 8-22 weeks after infection, likely caused by mounting immune pressure, were predictive of ensuing chronic infection, whereas stability was associated with resolution. Our study also showed that composition of HCV quasispecies may be preserved during transmission from host to host.
authors.affiliation: Department of Medicine, Mayo Clinic Scottsdale, Scottsdale, Arizona, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Laskus
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wilkinson
authors.forename: Juan F
authors.initials: JF
authors.lastname: Gallegos-Orozco
authors.forename: Marek
authors.initials: M
authors.lastname: Radkowski
authors.forename: Debra M
authors.initials: DM
authors.lastname: Adair
authors.forename: Marek
authors.initials: M
authors.lastname: Nowicki
authors.forename: Eva
authors.initials: E
authors.lastname: Operskalski
authors.forename: Zelma
authors.initials: Z
authors.lastname: Buskell
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Seeff
authors.forename: Hugo
authors.initials: H
authors.lastname: Vargas
authors.forename: Jorge
authors.initials: J
authors.lastname: Rakela
mesh_terms: D000328:Adult; D018562:Disease Transmission, Infectious; D019143:Evolution, Molecular; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000635:transmission / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013045:Species Specificity; D065227:Transfusion Reaction