The unique role of domain 2A of the hepatitis A virus precursor polypeptide P1-2A in viral morphogenesis.
The initial step during assembly of the hepatitis A virus particle is driven by domain 2A of P1-2A, which is the precursor of the structural proteins. The proteolytic removal of 2A from particulate VP1-2A by an as yet unknown host enzyme presumably terminates viral morphogenesis. Using a genetic approach, we show that a basic amino acid residue at the C-terminus of VP1 is required for efficient particle assembly and that host proteases trypsin and cathepsin L remove 2A from hepatitis A virus particles in vitro. Analyses of insertion mutants in the C-terminus of 2A reveal that this part of 2A is important for liberation of P1-2A from the polyprotein. The data provide the first evidence that the VP1/2A junction is involved in both viral particle assembly and maturation and, therefore, seems to coordinate the first and last steps in viral morphogenesis.
Morace
Graziella
G
Department MIPI, Istituto Superiore di Sanita, Rome, Italy. graziella.morace@iss.it
Kusov
Yuri
Y
Dzagurov
Georgy
G
Beneduce
Francesca
F
Gauss-Muller
Verena
V
D000595:Amino Acid Sequence; D002460:Cell Line; D030041:Hepatitis A virus / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010447:Peptide Hydrolases / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D019065:Virus Assembly / Q000502:physiology*; D014779:Virus Replication
D011498:Protein Precursors; D015678:Viral Structural Proteins; D010447:Peptide Hydrolases