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Flow Virometry to Analyze Antigenic Spectra of Virions and Extracellular Vesicles
Published on: January 25, 2017
Influence of pr-M cleavage on the heterogeneity of extracellular dengue virus particles
Jiraphan Junjhon1, Thomas J Edwards, Utaiwan Utaipat
1Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Abstract:
During dengue virus replication, an incomplete cleavage of the envelope glycoprotein prM, generates a mixture of mature (prM-less) and prM-containing, immature extracellular particles. In this study, sequential immunoprecipitation and cryoelectron microscopy revealed a third type of extracellular particles, the partially mature particles, as the major prM-containing particles in a dengue serotype 2 virus. Changes in the proportion of viral particles in the pr-M junction mutants exhibiting altered levels of prM cleavage suggest that the partially mature particles may represent an intermediate subpopulation in the virus maturation pathway. These findings are consistent with a model suggesting the progressive mode of prM cleavage.
Insights
Researchers discovered partially mature dengue virus particles, an intermediate form during maturation. This finding supports a progressive model of dengue virus prM protein cleavage and maturation.
Area of Science:
- Virology
- Structural Biology
- Molecular Biology
Background:
- Dengue virus replication involves the maturation of immature viral particles.
- Incomplete cleavage of the precursor membrane (prM) glycoprotein results in a mix of mature and immature extracellular dengue virus particles.
Purpose of the Study:
- To identify and characterize novel extracellular particle populations during dengue virus serotype 2 replication.
- To investigate the role of partially mature particles in the dengue virus maturation pathway.
Main Methods:
- Sequential immunoprecipitation assays to isolate specific viral particle populations.
- Cryo-electron microscopy (cryo-EM) for high-resolution structural analysis.
- Analysis of prM junction mutants with altered prM cleavage levels.
Main Results:
- Identification of a third type of extracellular particle, termed 'partially mature particles', in dengue serotype 2 virus.
- Partially mature particles were found to be the predominant prM-containing extracellular form.
- Observed shifts in the proportion of partially mature particles in prM junction mutants correlated with prM cleavage efficiency.
Conclusions:
- Partially mature particles represent a significant intermediate subpopulation in the dengue virus maturation process.
- The findings support a progressive model for the cleavage of the prM protein during dengue virus maturation.
- This study refines our understanding of the structural and dynamic aspects of flavivirus particle maturation.
