PHENOTYPIC MIXING OF RODENT BUT NOT AVIAN HEPADNAVIRUS SURFACE-PROTEINS INTO HUMAN HEPATITIS-B VIRUS-PARTICLES

The virus family Hepadnaviridae comprises two genera: orthohepadnaviru ses isolated from humans (hepatitis B virus [HBV]) and rodents (e.g., woodchuck hepatitis virus [WHV]) and avihepadnaviruses isolated from b irds (e.g., duck hepatitis B virus [DHBV]). They carry in their envelo pes two (DHBV) or three (HBV and WHV) coterminal proteins referred to as small (S), middle (M), or large (L) surface protein. These proteins are also secreted from infected cells as subviral particles consistin g of surface protein and lipid (e.g,, 20-nm hepatitis B surface antige n far HBV). To investigate the assembly of these proteins, we asked wh ether surface proteins from different hepadnaviruses are able to mix p henotypically with each other. By coexpression and coimmunoprecipitati on with species-specific antibodies, we could show the formation of mi xed subviral particles and disulfide-linked heterodimers between the W HV S and HBV M proteins whereas the DHBV and HBV surface proteins did not coassemble. Complementation of HBV genomes defective in expressing the S or L protein and therefore incompetent to form virions was poss ible with the closely related WHV S protein or a WKV pre-S-HBV S chime ra, respectively, but not with the less related DHBV S or L protein or with a DHBV L-HBV S chimera. The results suggest that the assembly of HBV subviral particles and virion envelopes requires relatively preci se molecular interactions of their surface proteins,,which are not con served between the two hepadnavirus genera. This contrasts with the ab ility of, e.g., rhabdoviruses or retroviruses, to incorporate envelope proteins even from unrelated viruses.