title: Mutational profiling of the variability of individual amino acid positions in the hepatitis B virus matrix domain.
abstract: The hepatitis B virus (HBV) is formed by budding. A stretch of 22 amino acids (aa) (matrix domain, MD, R103 - S124) in the large envelope protein L is crucial for virion formation and probably establishes contact to the nucleocapsid. Here, we assess the impact of sequence variations at numerous individual aa positions within the MD on virion formation. We generated panels of L mutants covering all 19 possible aa for 11 positions and tested the capacity of these mutants to rescue virus production by an L-defective HBV genome. At four positions (L112, R113, P117, W122), any replacement of the wild type (WT) aa reduced virus assembly to undetectable levels. Virus production was strongly diminished by substitutions at five other positions (R103, T106, S115, H116, A119). Only two tested positions (D114, Q118) tolerated several substitutions. The restricted positions may represent promising targets for the development of novel antiviral strategies.
authors.affiliation: Institute of Virology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Schittl
authors.affiliation: Institute of Virology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany. Electronic address: volker.bruss@helmholtz-muenchen.de.
authors.forename: Volker
authors.initials: V
authors.lastname: Bruss
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D014759:Viral Envelope Proteins
keywords: Envelopment; Hepatitis B virus; Large surface protein; Matrix domain