How the overlapping between HBV RT- and HBsAg-gene modulates the extent of HBV genetic-variability is still an open question. The rate of nucleotide-conservation (<1% variability) followed an atypical pattern in RT-gene, due to RT/HBsAg-overlapping (69.9% vs. 41.1% non-overlapping; p<0.001), consequent to the lower rate of synonymous-substitution within overlapping-region (median[IQR]dS=3.1[1.5-7.4] vs. 20.1[10.6-30.0]; p=3.249•10-22). The most conserved RT-regions were located within the YMDD-motif and the N-terminal parts of the palm- and finger-domain, critical for RT-functionality. These regions also corresponded to highly conserved HBsAg-domains critical for HBsAg-secretion. Conversely, the genomic-region encoding the HBsAg antigenic-loop (where immune-escape mutations are localized) showed a sharp decrease in the extent of conservation (40.6%), less pronounced in the setting of HIV-driven immune-suppression (48.8% vs. 21.5% in mono-infected;p=0.020). In conclusion, the overlapping reading-frame and the immune-system have shaped the patterns of RT and HBsAg genetic-variability. Highly conserved regions in RT and HBsAg may deserve further attention as novel therapeutic-targets.
Cento, V., Mirabelli, C., Dimonte, S., Salpini, R., Han, Y., Trimoulet, P., et al. (2012). Overlapping structure of HBV genome and immune selection pressure are critical forces modulating HBV evolution. JOURNAL OF GENERAL VIROLOGY [10.1099/vir.0.046524-0].
Overlapping structure of HBV genome and immune selection pressure are critical forces modulating HBV evolution
Salpini, R;BERTOLI, ADA;CECCHERINI SILBERSTEIN, FRANCESCA;PERNO, CARLO FEDERICO;Svicher, V.
2012-10-10
Abstract
How the overlapping between HBV RT- and HBsAg-gene modulates the extent of HBV genetic-variability is still an open question. The rate of nucleotide-conservation (<1% variability) followed an atypical pattern in RT-gene, due to RT/HBsAg-overlapping (69.9% vs. 41.1% non-overlapping; p<0.001), consequent to the lower rate of synonymous-substitution within overlapping-region (median[IQR]dS=3.1[1.5-7.4] vs. 20.1[10.6-30.0]; p=3.249•10-22). The most conserved RT-regions were located within the YMDD-motif and the N-terminal parts of the palm- and finger-domain, critical for RT-functionality. These regions also corresponded to highly conserved HBsAg-domains critical for HBsAg-secretion. Conversely, the genomic-region encoding the HBsAg antigenic-loop (where immune-escape mutations are localized) showed a sharp decrease in the extent of conservation (40.6%), less pronounced in the setting of HIV-driven immune-suppression (48.8% vs. 21.5% in mono-infected;p=0.020). In conclusion, the overlapping reading-frame and the immune-system have shaped the patterns of RT and HBsAg genetic-variability. Highly conserved regions in RT and HBsAg may deserve further attention as novel therapeutic-targets.Questo articolo è pubblicato sotto una Licenza Licenza Creative Commons
