Peculiarities in the designations of hepatitis B virus genes, their products, and their antigenic specificities: a potential source of misunderstandings

Abstract

The nomenclature of the hepatitis B virus (HBV) genes and their products has developed stepwise, occasionally in an erratic way, creating many misunderstandings, especially among those who do not know the structure of HBV and its genome in detail. One of the most frequent misunderstandings, even presented in leading journals, is the designation of HBV "e"-antigen as envelope or early antigen. Another problem area are the so-called "pre" regions in the HBV genome present upstream of both the core and the surface genes of HBV, inadvertently suggesting that they may be a part of corresponding precursor proteins. Misnomers and misclassifications are frequent in defining the subgenotypes and serological subtypes of HBV. Even the well-established terminology for HBV surface (HBs) or HBV core (HBc) antigen deviates from the conventional virological nomenclature for viral envelopes or capsid proteins/antigens, respectively. Another matter of undesirable variability between publications is the numbering of the nucleotides and the graphical representation of genomic maps. This editorial briefly explains how the nomenclature evolved, what it really means, and suggests how it could be adapted to today's knowledge.

Keywords: HBV; HBeAg; HBsAg; Subgenotypes; Subtypes; pre-C; pre-S.

Fig. 1

Suggested revised nomenclature for HBeAg and HBs genes, transcripts, proteins, and antigens. a HBV genome map with standard nomenclature taken from Ref. [83] showing the four open reading frames, their subregions, and some functions of the derived proteins on the outside. The black circles correspond to the various mRNAs, the inner closed circles show the cccDNA with enhancer I and II and the glucocorticoid response element (GRE). The EcoRI site is at the 12 h position. b Suggested revision of nomenclature for pre-S1, pre-S2, S domains, and pre-C sequence with corresponding mRNAs and map position of some major HBV gene functions. Note that LHBs, MHBs, and SHBs proteins have different N-termini within one ORF, but all run to a common C-terminus. The HBeAg precursor, the pre-pro-protein contains the pre-E signal peptide and the RNA packaging domain, both of which are removed during proteolytic processing. The mRNA for core protein and polymerase starts downstream of the start codon of the HBeAg pre-pro-protein and functions as the pregenomic RNA (pgRNA), which is encapsidated and reverse transcribed. The core (HBcAg) protein does not contain the pre-E signal peptide and is not glycosylated