Excel · study · 2026
Time-dependent processing of dengue virus polyprotein yields multiple capsid forms that disrupt cellular homeostasis
Listed in NCBI GEO
Dengue virus infections spread to new geographical regions every year, cause significant morbidity and mortality, yet the progress in drug/vaccine development is limited due to an incomplete understanding of its life cycle.
Description
While a few of the proteins coded by this virus exist in multiple forms, the sequential events of polyprotein processing to yield them and the consequential effects on host cells are unclear. In this study, the virus infected cell culture data suggest that the polyprotein undergoes a time-dependent processing to yield multiple capsid forms, ie, capsid, capsid-anchor, capsid-anchor-pr, capsid-anchor-prM.
Among them, the c-anc and c-anc-pr were found to localize to the mitochondria upon transfection into the HEK cells. The pulldown experiments indicate that c-anc also interacts with α1-syntrophin (SNTA1), a cytoplasmic protein that plays a role in redox potential, oxidative stress and mitochondrial biogenesis. Importantly, the mitostress analyses suggest that c-anc triggers impaired mitochondrial dysfunctions like potential, respiration and ATP generation.
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In this study, we also identify ursonic acid (UNA) as a c-anc binding compound that restores mitochondrial functions and suppresses virus multiplication in vitro, ex vivo and in mice. The revealed disrupted mitochondrial homeostasis appears to be common to DENV, ZIKV, JEV, YFV, HCV, ASFV and SARS-CoV-2; hence, UNA or its related compounds could be considered as inhibitors for the above virus infections.Whole-transcriptome sequencing was performed on four samples.
High-quality paired-end reads (6.64–9.70 Gb per sample) were generated on the Illumina platform using 2 × 150 bp chemistry. The reads were aligned to the Homo sapiens reference genome (GRCh38) using STAR (v2.7.10a) with default parameters. Mapping rates ranged from 91.09% (pEGFPNI vector-transfected HEK cells, replicate 2) to 94.18% (Capsid Anchor pGFP-transfected cells, replicate 1).
Differential expression analysis was carried out using the DESeq2 R package.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333382 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333382 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1471001 ncbi.nlm.nih.gov/bioproject/PRJNA1471001 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Sequencing 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE333382 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |