Hepatitis C virus quasispecies in chronically infected children subjected to interferon-ribavirin therapy.
Accumulating evidence suggests that certain features of hepatitis C virus (HCV), especially its high genetic variability, might be responsible for the low efficiency of anti-HCV treatment. Here, we present a bioinformatic analysis of HCV-1a populations isolated from 23 children with chronic hepatitis C (CHC) subjected to interferon-ribavirin therapy. The structures of the viral quasispecies were established based on a 132-amino-acid sequence derived from E1/E2 protein, including hypervariable region 1 (HVR1). Two types of HCV populations were identified. The first type, found in non-responders, contained a small number of closely related variants. The second type, characteristic for sustained responders, was composed of a large number of distantly associated equal-rank variants. Comparison of 445 HVR1 sequences showed that a significant number of variants present in non-responding patients are closely related, suggesting that certain, still unidentified properties of the pathogen may be key factors determining the result of CHC treatment.
Figlerowicz
Magdalena
M
Department of Infectious Diseases and Child Neurology, Karol Marcinkowski University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, Poland.
Jackowiak
Paulina
P
Formanowicz
Piotr
P
Kędziora
Paweł
P
Alejska
Magdalena
M
Malinowska
Nelli
N
Błażewicz
Jacek
J
Figlerowicz
Marek
M
D000293:Adolescent; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014759:Viral Envelope Proteins / Q000235:genetics
D000998:Antiviral Agents; D004279:DNA, Viral; C087035:E1 protein, Hepatitis C virus; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D012254:Ribavirin