1887

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Volume 102, Issue 8

Increased capsid oligomerization is deleterious to dengue virus particle production No Access

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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): capsid , dengue virus , pseudoinfectious virus and trans-complementation
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
© 2021 The Authors
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/content/journal/jgv/10.1099/jgv.0.001635
2021-08-19
2024-05-08
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Increased capsid oligomerization is deleterious to dengue virus particle production
J. Gen. Virol. 102, 001635 (2021); https://doi.org/10.1099/jgv.0.001635
/content/journal/jgv/10.1099/jgv.0.001635
/content/journal/jgv/10.1099/jgv.0.001635
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