Journal
JOURNAL OF GENERAL VIROLOGY
Volume 100, Issue 12, Pages 1663-1673Publisher
MICROBIOLOGY SOC
DOI: 10.1099/jgv.0.001346
Keywords
dengue virus; capsid anchor; polyprotein processing; viral protease; host protease; domain swapping; positive strand RNA virus; Flaviviridae; DENV2; pseudovirus production
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Funding
- ICGEB post-doctoral fellowships
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The assembly and secretion of flaviviruses are part of an elegantly regulated process. During maturation, the viral polyprotein undergoes several co- and post-translational cleavages mediated by both viral and host proteases. Among these, sequential cleavage at the N and C termini of the hydrophobic capsid anchor (Ca) is crucial in deciding the fate of viral infection. Here, using a refined dengue pseudovirus production system, along with cleavage and furin inhibition assays, immunoblotting and secondary structure prediction analysis, we show that Ca plays a key role in the processing efficiency of dengue virus type 2 (DENV2) structural proteins and viral particle assembly. Replacement of the DENV2 Ca with the homologous regions from West nile or Zika viruses or, alternatively, increasing its length, improved cleavage and hence particle assembly. Further, we showed that substitution of the Ca conserved proline residue (P110) to alanine abolishes pseudovirus production, regardless of the Ca sequence length. Besides providing the results of a biochemical analysis of DENV2 structural polyprotein processing, this study also presents a system for efficient production of dengue pseudoviruses.
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