[Molecular virology of the hepatitis B virus]

The hepatitis B virus (HBV) belongs to the hepadnavirus family. The genome of the virus, formed by a small DNA molecule with 3,200 base pairs, has 4 strongly overlapping protein coding regions: ORF preS/S, corresponding to the envelope proteins that constitute the HBV surface antigen (HBsAg); ORF preC/C, which encodes the viral capsid component (core antigen or HBcAg) and a non-structural protein that, after postranslation modification, is secreted and constitutes the "e" antigen (HBeAg); ORF P, which encodes the viral polymerase (polyprotein with DNA polymerase activity, reverse transcriptase and RNAase), and ORF X, which encodes a protein that acts as a multifunctional regulator for both the viral and cell cycles. HBV has a mutation rate of 1.4-3.2 x 105 substitutions/nucleotide/year. As a result of this variability, the virus circulates as a complex mixture of genetic variants, constituting a semi-species, that evolves throughout the infection depending on the evolutionary pressure of factors such as the immune response and antiviral treatments. Based on this variability, HBV has been classified into 8 genotypes (A-H) defined by a difference of more than 8% in the sequences of the complete viral genome. This variability is also responsible for HBV resistance to antiviral treatments with nucleotide and nucleoside analogs. Diagnosis of HBV infection includes determination of virological markers: viral antigens (HBsAg, HBeAg), specific antibodies (anti-HBc, anti-HBe, anti-HBs) and study of HBV-DNA for its detection and quantification and determination of genotypes and viral variants.