Overlapping structure of hepatitis B virus (HBV) genome and immune selection pressure are critical forces modulating HBV evolution

Valeria Cento, Carmen Mirabelli, Salvatore Dimonte, Romina Salpini, Yue Han, Pascale Trimoulet, Ada Bertoli, Valeria Micheli, Guido Gubertini, Giuseppina Cappiello, Alberto Spanò, Roberta Longo, Martina Bernassola, Francesco Mazzotta, Giuseppe Maria De Sanctis, Xin Xin Zhang, Jens Verheyen, Antonella D Arminio Monforte, Francesca Ceccherini-Silberstein, Carlo Federico PernoValentina Svicher

Research output: Contribution to journalArticlepeer-review


How the overlap between the hepatitis B virus (HBV) reverse transcriptase (RT) and HBV S antigen (HBsAg) genes modulates the extent of HBV genetic variability is still an open question, and was investigated here. The rate of nucleotide conservation (≤1% variability) followed an atypical pattern in the RT gene, due to an overlap between RT and HBsAg (69.9% nucleotide conservation in the overlapping region vs 41.2% in the non-overlapping region; P-22]. The most conserved RT regions were located within the YMDD motif and the N-terminal parts of the palm and finger domains, critical for RT functionality. These regions also corresponded to highly conserved HBsAg domains that are 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 %), which was less pronounced in the setting of human immunodeficiency virus (HIV)-driven immune suppression (48.8% in HIV-HBV coinfection vs 21.5% in mono-infected patients; P50.020). In conclusion, the overlapping reading frame and the immune system appear to 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.

Original languageEnglish
Pages (from-to)143-149
Number of pages7
JournalJournal of General Virology
Issue numberPART11
Publication statusPublished - Jan 1 2013

ASJC Scopus subject areas

  • Virology


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