An Integrated Systems Biology Approach Identifies the Proteasome as A Critical Host Machinery for ZIKV and DENV Replication.
Genomics Proteomics Bioinformatics
; 19(1): 108-122, 2021 02.
Article
in En
| MEDLINE
| ID: mdl-33610792
ABSTRACT
The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus-host protein-protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for further studies of flavivirus-host interactions, disease pathogenesis, and new drug targets.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dengue
/
Dengue Virus
/
Proteasome Endopeptidase Complex
/
Zika Virus
/
Zika Virus Infection
Limits:
Humans
Language:
En
Journal:
Genomics Proteomics Bioinformatics
Journal subject:
BIOQUIMICA
/
GENETICA
/
INFORMATICA MEDICA
Year:
2021
Document type:
Article
Affiliation country: