A genome-wide RNAi screen reveals common host-virus gene signatures: Implication for dengue antiviral drug discovery Journal Article
| Authors: | Shum, D.; Bhinder, B.; Mahida, J.; Radu, C.; Calder, P. A.; Djaballah, H. |
| Article Title: | A genome-wide RNAi screen reveals common host-virus gene signatures: Implication for dengue antiviral drug discovery |
| Abstract: | Dengue is the most common mosquito-borne viral disease that in recent years has become a major international public health concern. Dengue is a tropical neglected disease with increasing global incidences, affecting millions of people worldwide, and without the availability of specific treatments to combat it. The identification of host-target genes essential for the virus life cycle, for which effective modulators may already exist, would provide an alternative path to a rapid drug development of the much needed antidengue agents. For this purpose, we performed the first genome-wide RNAi screen, combining two high-content readouts for dengue virus infection (DENV E infection intensity) and host cell toxicity (host cell stained nuclei), against an arrayed lentiviral-based short hairpin RNA library covering 16,000 genes with a redundancy of at least 5 hairpins per gene. The screen identified 1924 gene candidates in total; of which, 1730 gene candidates abrogated dengue infection, whereas 194 gene candidates were found to enhance its infectivity in HEK293 cells. A first pass clustering analysis of hits revealed a well-orchestrated gene-network dependency on host cell homeostasis and physiology triggering distinct cellular pathways for infectivity, replication, trafficking, and egress; a second analysis revealed a comprehensive gene signature of 331 genes common to hits identified in 28 published RNAi host-viral interaction screens. Taken together, our findings provide novel antiviral molecular targets with the potential for drug discovery and development. |
| Keywords: | core protein; infection; liver; egfr; cells; activation; pathway; replication; mitochondrial; entry |
| Journal Title: | Gen Biotechnology |
| Volume: | 2 |
| Issue: | 2 |
| ISSN: | 2768-1572 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 2023-04-01 |
| Start Page: | 133 |
| End Page: | 148 |
| Language: | English |
| ACCESSION: | WOS:001136593200005 |
| DOI: | 10.1089/genbio.2023.0001 |
| PROVIDER: | wos |
| PMCID: | PMC10623629 |
| PUBMED: | 37928776 |
| Notes: | Article -- Source: Wos |
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