O-20 MOLECULAR AND BIOLOGICAL CHARACTERIZATION OF HEPATITIS B VIRUS SUBGENOTYPE F1b CLUSTERS: UNRAVELING ITS ROLE IN HEPATOCARCINOGENESIS

Abstract

Introduction and Objectives: Hepatitis B virus subgenotype F1b infection has been associated with the early occurrence of hepatocellular carcinoma in chronically infected patients from Alaska and Peru. In Argentina, however, despite the high prevalence of subgenotype F1b infection, this relationship has not been described. This study aimed to unravel the observed differences in the progression of the infection, and an in-depth molecular and biological characterization of the subgenotype F1b was performed. Materials and Methods: 99 subgenotype F1b full-length sequences were obtained, and phylogeny was addressed by the maximum likelihood method. The replicative capacity of the subgenotype F1b clones was assessed by qPCR, Southern and Northern blot analysis. Antigen expression was detected by electrochemiluminescence and Western blot. The analysis of signaling pathways associated with hepatocarcinogenesis was assessed by RT-qPCR. Results: Phylogenetic analysis of subgenotype F1b genomes revealed the existence of two highly supported clusters. One of the clusters, designated as gtF1b Basal included sequences mostly from Alaska, Peru, and Chile, while the other, called gtF1b Cosmopolitan, contained samples mainly from Argentina and Chile. The clusters were characterized by a differential signature pattern of eight nucleotides distributed throughout the genome. In vitro characterization of representative clones from each cluster revealed major differences in viral RNA levels, virion secretion, and antigen expression levels. Interestingly, differential regulation in the expression of genes associated with tumorigenesis was also identified. Conclusions: This study provides new insights into the molecular and biological characteristics of the subgenotype F1b clusters and contributes to unraveling the different clinical outcomes of subgenotype F1b chronic infections.