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Processing of dengue type 4 and other flavivirus nonstructural proteins

  • C.-J. Lai
  • M. Pethel
  • L. R. Jan
  • H. Kawano
  • A. Cahour
  • B. Falgout
Conference paper
Part of the Archives of Virology Supplementum book series (ARCHIVES SUPPL, volume 9)

Summary

Dengue type 4 (DEN4) and other flaviviruses employ host and viral proteases for polyprotein processing. Most proteolytic cleavages in the DEN4 nonstructural protein (NS) region are mediated by the viral NS2B-NS3 protease. The N-terminal third of NS3, containing sequences homologous to serine protease active sites, is the protease domain. To determine required sequences in NS2B, deletions were introduced into DEN4 NS2B-30%NS3 cDNA and the expressed polyproteins assayed for self-cleavage. A 40 amino acid segment within NS2B was essential. Sequence analysis of NS2B predicts that this segment constitutes a hydrophilic domain surrounded by hydrophobic regions. Hydophobicity profiles of other flavivirus NS2Bs show similar patterns. Cleavage of DEN4 NS1-NS2A requires an octapeptide sequence at the NS1 C terminus and downstream NS2A. Comparison of the analogous octapeptide sequences among flaviviruses indicates a consensus cleavage sequence of (P8)/Met/Leu-Val-Xaa-Ser-Xaa-Val-Ala(P1), where Xaa are non- conserved amino acids. The effects on cleavage of amino acid substitutions in this consensus sequence were analyzed. Most substitutions of the conserved residues interfered with cleavage, whereas substitutions of non-conserved residues had little or no effect. These findings indicate that the responsible enzyme recognizes well-defined sequences at the cleavage site.

Keywords

Dengue Virus Nonstructural Protein Japanese Encephalitis Virus Yellow Fever Virus Amino Acid Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • C.-J. Lai
    • 1
  • M. Pethel
    • 1
  • L. R. Jan
    • 1
  • H. Kawano
    • 1
  • A. Cahour
    • 1
  • B. Falgout
    • 1
  1. 1.Molecular Viral Biology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA

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