Functions of the Large Hepatitis B Virus Surface Protein in Viral Particle Morphogenesis

Abstract

The hepatitis B virus (HBV) envelope and the subviral lipoprotein particles contain three viral surface proteins (L, M, and S) which are expressed from one open reading frame by the usage of three start codons and a common stop codon. The largest surface protein L has some unusual properties. It adopts two different transmembrane topologies due to a posttranslational switch of the folding in approximately half of the L proteins. L molecules which expose their N-terminal preSl domain on the viral particle surface are probably ligands for a putative virus receptor and determine the species specificity and liver tropism of this virus. L chains with internal preSl domains are required in virion morphogenesis and mediate the contact to the nucleocapsid like a matrix protein. Overexpression of this form of the L protein is also responsible for the inhibition of viral particle release. This short review summarizes our knowledge on the biosynthesis and maturation of the HBV surface proteins and their functions in viral particle morphogenesis with special emphasis on the L protein.

Novel Autoregulatory Function of Hepatitis B Virus M Protein on Surface Gene Expression

“…In vitro studies suggest that M protein is not essential for in vitro HBV replication (18), virion morphogenesis (19), or infectivity (20). Furthermore, because an M protein-deficient mutant can be found in patients with fulminant hepatitis, it was suggested that M protein is not required for in vivo viral replication (21).…”

“…The NotI site (underlined) is preceded by six random nucleotides and followed by an HBV sequence (nt 3188ϳ3207). The reverse primer used was (N) 6 GCGGCCGCTTA(X) 19 , where N and X represent random nucleotides and a bracketed HBV sequence, respectively. The NotI site (underlined) is followed by the stop codon (TTA).…”

“…The NotI site (underlined) is preceded by six random nucleotides and followed by a Kozak sequence (ACCATG) and an HBV sequence ((X) 17 ) corresponding to the bracketed amino acids. The PCR fragment was amplified with the forward primer and reverse primer (N) 6 GCGGCCGCTTA(X) 19 using plasmid p(3A)SAg as the template, digested with NotI, and ligated to the NotI-restricted and dephosphorylated pCMV-Basic vector.…”

“…The primers were designed to bracket the truncated proteins exactly; they spanned amino acids 1-281, 17 , where the NotI site (underlined) is preceded by N, which denotes the HBV sequences located nine nucleotides upstream of (X) 17 , and followed by the bracketed HBV sequence represented by (X) 17 . The reverse primer used was 5Ј-(N) 6 GCGGCCCGTTA(Y) 19 , where the NotI site (underlined) is preceded by N, which denotes the HBV sequences located 12 nucleotides downstream of (Y) 19 , and followed by the stop codon and the bracketed HBV nucleotides represented by (Y) 19 . Thus, HBV DNA sequences that correspond to nt 3213ϳ834 (pHAMHBs-(1-281)), 3213ϳ447 (pHA-MHBs-(1-152)), 3213ϳ219 (pHAMHBs-(1-76)), 3213ϳ204 (pHA-MHBs-(1-71)), 3213ϳ162 (pHA-MHBs-(1-57)), 3213ϳ156 (pHA-MHBs-(1-55)), 3213ϳ147 (pHA-pre-S2-(1-52)), 3213ϳ135 (pHA-pre-S2-(1-48)), 3213ϳ132 (pHA-pre-S2-(1-47)), 1ϳ156 (pHA-pre-S2-(4 -55)), 37ϳ156 (pHA-pre-S2-(16 -55)), and 46ϳ156 (pHA-pre-S2-(19 -55)) were amplified using the forward and reverse primers with plasmid p(3A)SAg as the template.…”

Packaging of up to 240 subunits of a 17 kDa nuclease into the interior of recombinant hepatitis B virus capsids

“…Virion morphogenesis starts with encapsidation by the capsid, or core, protein of a complex consisting of one of the viral RNAs, the reverse transcriptase, and probably cellular chaperones [5]. After reverse transcription, the DNA-containing nucleocapsid buds into a pre-Golgi compartment, exiting from the cell as enveloped virion [6].…”