Cis-preferential recruitment of duck hepatitis B virus core protein to the RNA/polymerase preassembly complex

Hepatology. 2002 Jan;35(1):209-16. doi: 10.1053/jhep.2002.30086.

Abstract

Hepadnaviral replication requires the concerted action of the polymerase and core proteins to ensure selective packaging of the RNA pregenome into nucleocapsids. Virus assembly is initiated by cis-preferential binding of polymerase to the encapsidation signal straightepsilon, present on pregenomic RNA. Using the duck hepatitis B virus (DHBV) model, we analyzed how core protein is recruited to the RNA/polymerase preassembly complex. Two sets of trans-complementation assays were performed in cotransfected hepatoma cells. First, a replication-competent DHBV construct was tested for its ability to rescue replication of genomes bearing mutations within the core region. Self-packaging of wild-type pregenomes was more efficient than cross-packaging of core-deficient pregenomes, and this bias was strongly enhanced if mutant pregenomes coded for self-assembly-competent, but packaging-deficient, core proteins. Second, the site of wild-type core protein translation, i.e., pregenomic RNA (cis) or separate messenger RNA (trans), was analyzed for its effect on the phenotype of a previously described dominant-negative (DN) DHBV core protein mutant. This mutant forms chimeric nucleocapsids with wild-type core proteins and blocks reverse transcription within most, but not all, mixed particles. Strikingly, suppression of viral DNA synthesis by the mutant increased 100-fold when wild-type core protein was provided in trans. Our results suggest that recruitment of core protein to the DHBV preassembly complex occurs in a cis-preferential manner. This mechanism may account for the leakiness of DN DHBV core protein mutants targeting reverse transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Blotting, Northern
  • Blotting, Southern
  • Blotting, Western
  • DNA, Viral / biosynthesis
  • DNA-Directed RNA Polymerases / metabolism*
  • Dimerization
  • Hepatitis B Virus, Duck / chemistry*
  • Hepatitis B Virus, Duck / physiology
  • Mutation
  • Nucleocapsid / metabolism
  • RNA, Messenger / metabolism
  • RNA, Viral / metabolism*
  • Transcription, Genetic
  • Viral Core Proteins / genetics
  • Viral Core Proteins / metabolism*
  • Virus Replication

Substances

  • DNA, Viral
  • RNA, Messenger
  • RNA, Viral
  • Viral Core Proteins
  • DNA-Directed RNA Polymerases