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Open AccessArticle

Hepatitis B Virus X Gene Differentially Modulates Subgenotype F1b and F4 Replication

1
Cátedra de Virología, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, Buenos Aires 1113, Argentina
2
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1425, Argentina
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(7), 655; https://doi.org/10.3390/v11070655
Received: 19 June 2019 / Revised: 12 July 2019 / Accepted: 16 July 2019 / Published: 18 July 2019
Hepatitis B virus (HBV) is classified into ten genotypes and numerous subgenotypes (sgt). In particular, sgt F1b and sgt F4, native of Latin America, have been associated with differences in clinical and virological characteristics. Hepatitis B virus X protein (HBx) is a multifunctional regulatory protein associated with the modulation of viral transcription and replication. In this work, we analyzed the role of the X gene and the encoded X protein in sgtF1b and sgtF4 replication. Transfection with HBx deficient genomes revealed remarkable differences in the replicative capacity of sgtF1b and sgtF4 mutants. The silencing of HBx increased sgtF1b X(-) transcription and replication by more than 2.5 fold compared to the wild type variant, while it decreased sgtF4 X(-) transcription and replication by more than 3 fold. Trans-complementation of HBx restore sgtF1b and sgtF4 wild type transcription and replication levels. In addition, transfection with chimeric variants, carrying wild type (F1b/XF4 and F4/XF1b) or mutated (F1b/X(-)F4 and F4/X(-)F1b) X gene of one sgt in the backbone of the other sgt, showed that the nucleotide sequence of the X gene, that includes regulatory elements that modulate pgRNA transcription, was responsible for the disparity observed between sgtF1b X(-) and sgtF4 X(-). These results showed that sgtF1b and sgtF4 X gene play a central role in regulating HBV transcription and replication, which eventually lead to a common purpose, to reach wild type replication levels of sgtF1b and sgtF4 viruses. View Full-Text
Keywords: Hepatitis B virus; X gene; X protein; subgenotype F1b; subgenotype F4; differential replication Hepatitis B virus; X gene; X protein; subgenotype F1b; subgenotype F4; differential replication
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Elizalde, M.M.; Speroni, M.; Campos, R.H.; Flichman, D.M. Hepatitis B Virus X Gene Differentially Modulates Subgenotype F1b and F4 Replication. Viruses 2019, 11, 655.

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