Detection of Hypermodified Middle-Envelope (M) Proteins Secreted from Naturally Occurring HBV Variants Containing a preS2 Internal Deletion

Human hepatitis B virus (HBV) produces three structurally related envelope proteins (also called surface antigens) from a single open reading frame (ORF) (Fig. 1). This ORF contains three in-frame translational initiation AUG codons, dividing it into three regions: preS1, preS2, and S (1,2). The three envelope proteins are referred to in the literature as large (L) (p39/gp42), middle (M) (gp33/gp36), and small (S, major surface antigen) (p24/gp27) envelope proteins. These proteins are co-carboxy-terminal proteins with different amino terminal extensions.