Variability of reverse transcriptase and overlapping S gene in hepatitis B virus isolates from untreated and lamivudine-resistant chronic hepatitis B patients.

Donatella Ferraro, Vito Di Marco, Rosa Di Stefano, Antonio Craxi, Graziella Isgrò, Sergio Maimone, Giovanni Raimondo, Santa Brancatelli, Teresa Pollicino, Giovanni Squadrito

Risultato della ricerca: Article

40 Citazioni (Scopus)

Abstract

BACKGROUND: The high degree of diversity of the hepatitis B virus (HBV) quasispecies in chronically infected individuals raises the possibility that HBV genetic variants favouring resistance to ucleoside/nucleotide analogues (NAs) might pre-exist to reatment. The aim of this study was to investigate the genetic variability of the entire HBV reverse transcriptase (RT) domain and of the overlapping S gene in a large series of untreated hepatitis B surface antigen carriers and in lamivudine (3TC)-resistant patients. METHODS: Sequencing analysis of the entire HBV RT domain of isolates from 100 untreated (treatment-naive group) and 59 3TC-resistant (3TC-resistant group) consecutive patients with chronic hepatitis B was performed. RESULTS: In the treatment-naive group, primary mutations known to cause resistance to NAs were not detected, but variably combined secondary/compensatory mutations were found in 46 (46%) patients. Moreover, four patients carried mutations that modified the S protein antigenicity. In the 3TC-resistant group, besides the primary 3TC-resistant mutations, various combinations of primary and secondary mutations conferring resistance to other NAs were detected in 41/59 (69.5%) patients. Importantly, the RT mutations induced by 3TC provoked stop codons in the overlapping S gene in two patients and modified the S protein antigenicity in another nine. CONCLUSIONS: This study shows that HBV mutants associated with resistance to NAs might already be present as the major infecting population in untreated patients, and that variants emerging under 3TC might also carry mutations favouring resistance to other NAs and/or potentially altering the S protein immunoreactivity.
Lingua originaleEnglish
pagine (da-a)649-654
Numero di pagine6
RivistaAntiviral Therapy
Volume14
Stato di pubblicazionePublished - 2009

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Entra nei temi di ricerca di 'Variability of reverse transcriptase and overlapping S gene in hepatitis B virus isolates from untreated and lamivudine-resistant chronic hepatitis B patients.'. Insieme formano una fingerprint unica.

  • Cita questo