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Comparative Study
. 2006 Dec 14:3:103.
doi: 10.1186/1743-422X-3-103.

Comparative analysis of hepatitis C virus phylogenies from coding and non-coding regions: the 5' untranslated region (UTR) fails to classify subtypes

Peter T Hraber  1 , William Fischer, William J Bruno, Thomas Leitner, Carla Kuiken
Affiliations
Comparative Study

Comparative analysis of hepatitis C virus phylogenies from coding and non-coding regions: the 5' untranslated region (UTR) fails to classify subtypes

Peter T Hraber et al. Virol J. .

Abstract

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.

Conclusion: 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.

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Figures

Figure 1
Figure 1
Neighbor-joining phylogenies. Unrooted neighbor-joining phylogenetic trees from (a) complete HCV genome, (b) polyprotein, (c) 5' UTR, and (d) the Okamoto region of NS5B. Due to our focus on the consistency of subtype classification and the relative branching topology among subtypes, each tree is scaled independently.
Figure 2
Figure 2
Maximum-likelihood phylogenies. Unrooted maximum likelihood phylogenetic trees from (a) complete HCV genome, (b) polyprotein, (c) 5' UTR, and (d) the Okamoto region of NS5B. Taxon labels indicate HCV genotype and subtype from Table 1. Due to our focus on the consistency of subtype classification and the relative branching topology among subtypes, each tree is scaled independently.
Figure 3
Figure 3
Consistency and homoplasy indices. Moving-window averages of (a) character consistency with the whole-genome phylogeny for windows of 100 (red), 300 (blue), or 500 (black) nucleotides and (b) proportion of informative sites (red) and rescaled homoplasy index (black) for windows of 100 nucleotides as a function of the window midpoint in the whole-genome alignment. Regions corresponding to the 5' UTR (left) and NS5B (right) are indicated with grey bands, with a white band in the middle of NS5B to indicate the 329 nt Okamoto region.
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