Comparative analysis of hepatitis C virus phylogenies from coding and non-coding regions: the 5' untranslated region (UTR) fails to classify subtypes.
BACKGROUND
The duration of treatment for HCV infection is partly indicated by the genotype of the virus. For studies of disease transmission, vaccine design, and surveillance for novel variants, subtype-level classification is also needed. This study used the Shimodaira-Hasegawa test and related statistical techniques to compare phylogenetic trees obtained from coding and non-coding regions of a whole-genome alignment for the reliability of subtyping in different regions.


RESULTS
Different regions of the HCV genome yield inconsistent phylogenies, which can lead to erroneous conclusions about classification of a given infection. In particular, the highly conserved 5' untranslated region (UTR) yields phylogenetic trees with topologies that differ from the HCV polyprotein and complete genome phylogenies. Phylogenetic trees from the NS5B gene reliably cluster related subtypes, and yield topologies consistent with those of the whole genome and polyprotein.


CONCLUSIONS
These results extend those from previous studies and indicate that, unlike the NS5B gene, the 5' UTR contains insufficient variation to resolve HCV classifications to the level of viral subtype, and fails to distinguish genotypes reliably. Use of the 5' UTR for clinical tests to characterize HCV infection should be replaced by a subtype-informative test.
Hraber
Peter T
PT
Theoretical Biology and Biophysics, T-10 MS K710, Los Alamos National Laboratory, Los Alamos NM 87545, USA. phraber@lanl.gov
Fischer
William
W
Bruno
William J
WJ
Leitner
Thomas
T
Kuiken
Carla
C
D020121:5' Untranslated Regions / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D016679:Genome, Viral; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics; D006801:Humans; D010802:Phylogeny; D020815:Polyproteins / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics; D014773:Virology / Q000379:methods; D012324:RNA-Dependent RNA Polymerase
D020121:5' Untranslated Regions; D004279:DNA, Viral; D020815:Polyproteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase