Distinctive properties of the hepatitis B virus envelope proteins

Abstract

Using recombinant adenoviral vectors, we expressed and characterized the large, middle, and major envelope proteins of hepatitis B virus (HBV). Cells infected with the recombinant adenovirus which contained the large envelope gene (HS1.HP) expressed predominantly large envelope and small but detectable quantities of middle (4%) and major (6%) envelope proteins in the cell lysate. No HBV envelope proteins were detected in the culture medium from HS1.HP-infected cells. Cells infected with a recombinant adenovirus which contained the middle envelope gene (HS2.HP) expressed and secreted the middle and major envelope proteins in a molar ratio of 3:1. Cells infected with the recombinant adenovirus which contained the major envelope gene (HS.HP) expressed and secreted major envelope proteins. The HBV envelope proteins secreted by cells infected with either HS2.HP or HS.HP were assembled in 22-nm particles, as shown by velocity sedimentation rate determination, buoyant densities, and electron microscopy. Cells coinfected with a recombinant adenovirus which contained the large envelope gene and with either HS2.HP or HS.HP expressed similar quantities of the large, middle, and major envelope proteins in the cell lysates. Secretion of the major and middle envelope proteins was inhibited more than 95% by the presence of the large envelope proteins. These results suggest that differential biosynthesis, transport, and processing of the envelope proteins occur during HBV infection, allowing efficient assembly and secretion of virions and hepatitis B surface antigen particles.

Experimental systems for the study of hepadnavirus and hepatitis delta virus infections

“…Combining these observations, Chisari and colleagues (64, 76,77) concluded that overproduction of pre-S1 inhibits secretion of all envelope glycoproteins. A similar conclusion has been reached by investigators studying expression of these proteins in cultured cells transfected with fragments of HBV DNA (45, [78][79][80][81]. The consequences of this inhibition are, in time, dramatic.…”

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

“…In addition to the N-glycosylation site in the preS2 domain, the preS2 domain can be partially O-glycosylated, depending on the genotype and the presence of the threonine (T37) ( Figure 1B) [73]. Similar to HBsAgS, HBsAgM proteins assemble into SVPs and can be secreted independently from other viral proteins [74][75][76][77]. HBsAgM, however, is not essential for virion morphogenesis and infectivity [78].…”

Activation of hepatitis B virus S promoter by the viral large surface protein via induction of stress in the endoplasmic reticulum

“…In addition, the middle and/or small forms, in the absence of other viral proteins, can bud into the lumen and be secreted in the form of spherical and filamentous subviral particles. LS, in contrast, cannot be secreted when expressed alone but instead is retained within the cell in the form of intraluminal particles (3,4,17,20,22,33). If LS is coexpressed with the other forms of surface protein, they form heteromultimers whose phenotype depends on the relative amounts of the various surface proteins: a small relative amount of LS results in secretion, while a large amount results in retention.…”