1887

Abstract

The capsid protein (C) of dengue virus is required for viral infectivity as it packages viral RNA genome into infectious particles. C exists as a homodimer that forms via hydrophobic interactions between the α2 and α4 helices of monomers. To identify C region(s) important for virus particle production, a complementation system was employed in which single-round infectious particles are generated by -encapsidation of a viral C-deleted genome by recombinant C expressed in mosquito cells. Mutants harbouring a complete α3 deletion, or a dual Ile65-/Trp69-to-Ala substitution in the α3 helix, exhibited reduced production of infectious virus. Unexpectedly, higher proportions of oligomeric C were detected in cells expressing both mutated forms as compared with the wild-type counterpart, indicating that the α3 helix, through its internal hydrophobic residues, may down-modulate oligomerization of C during particle formation. Compared with wild-type C, the double Ile65-/Trp69 to Ala mutations appeared to hamper viral infectivity but not C and genomic RNA incorporation into the pseudo-infectious virus particles, suggesting that increased C oligomerization may impair DENV replication at the cell entry step.

Funding
This study was supported by the:
  • Siriraj Foundation (Award D003526)
    • Principle Award Recipient: - SangiambutSutha
  • National Center for Genetic Engineering and Biotechnology, Bangkok, Thailand (Award P-17-51296)
    • Principle Award Recipient: Sutha- Sangiambut
  • The Thailand Research Fund (Award RSA 6080002)
    • Principle Award Recipient: Sutha- Sangiambut
  • The Research Chair Grant, from the National Science and Technology Development Agency (Award P-16-50392)
    • Principle Award Recipient: PridaMalasit
  • The Senior Research Scholarship from Thailand Research Fund (Award RTA 6180013)
    • Principle Award Recipient: NoppornSittisombut
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/content/journal/jgv/10.1099/jgv.0.001635
2021-08-19
2024-12-12
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