Hepatitis C hypervariable region 1: association of reduced selection pressure in african americans with treatment failure.
In a prospective therapeutic trial, features of the hepatitis C quasispecies were investigated as possible markers of therapeutic response. Individuals chronically infected with hepatitis C genotype 1 received antiviral therapy consisting of alpha-interferon plus ribavirin. The study targeted the most rapidly evolving segment of the viral genome, hypervariable region 1 within the envelope-2 gene. Among individuals failing to clear virus in response to therapy, significant differences were observed between quasispecies of African-American and Caucasian subjects. While distance measures for synonymous substitutions were similar between racial subgroups, measures of distance at the amino acid level (nonsynonymous substitutions) varied significantly. Taken together, the observed patterns of variability corresponded to reduced host selection pressure against hypervariable region 1 in African-American nonresponders. Reduced selection pressure was present at baseline and persisted through treatment and follow-up, suggesting population stratification of host factors that influence selection pressure on hepatitis C virus.
Park
Vicki M
VM
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. vpark@utmem.edu
Mason
Barbara C
BC
Krushkal
Julia
J
Li
Rongling
R
Riely
Caroline
C
Fleckenstein
Jaquelyn
J
D000328:Adult; D001741:Black or African American; D000998:Antiviral Agents / Q000627:therapeutic use; D004337:Drug Carriers; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D012641:Selection, Genetic; D013714:Tennessee / Q000453:epidemiology; D017211:Treatment Failure; D014764:Viral Proteins / Q000187:drug effects / Q000235:genetics*
D000998:Antiviral Agents; D004337:Drug Carriers; C400562:HVR1 protein, Hepatitis C virus; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D014764:Viral Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a