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Updated: Jun 5, 2026
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Comparative RNAi screening reveals host factors involved in enterovirus infection of polarized endothelial monolayers
Carolyn B Coyne1, Rebecca Bozym, Stefanie A Morosky
1Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. coynec2@pitt.edu
Abstract:
Enteroviruses, including coxsackievirus B (CVB) and poliovirus (PV), can access the CNS through the blood brain barrier (BBB) endothelium to cause aseptic meningitis. To identify cellular components required for CVB and PV infection of human brain microvascular endothelial cells, an in vitro BBB model, we performed comparative RNAi screens and identified 117 genes that influenced infection. Whereas a large proportion of genes whose depletion enhanced infection (17 of 22) were broadly antienteroviral, only 46 of the 95 genes whose depletion inhibited infection were required by both CVB and PV and included components of cell signaling pathways such as adenylate cyclases. Downregulation of genes including Rab GTPases, Src tyrosine kinases, and tyrosine phosphatases displayed specificity in their requirement for either CVB or PV infection. These findings highlight the pathways hijacked by enteroviruses for entry and replication in the BBB endothelium, a specialized and clinically relevant cell type for these viruses.
Insights
Researchers identified 117 genes affecting enterovirus infection of the blood-brain barrier (BBB) endothelium. Specific cellular pathways were found to be crucial for coxsackievirus B (CVB) and poliovirus (PV) entry and replication, offering insights into aseptic meningitis.
Area of Science:
- Neuroscience
- Virology
- Cell Biology
Background:
- Enteroviruses, such as coxsackievirus B (CVB) and poliovirus (PV), can infect the central nervous system (CNS) by crossing the blood-brain barrier (BBB).
- Understanding the cellular mechanisms governing viral entry and replication at the BBB endothelium is crucial for developing therapeutic strategies against viral meningitis.
Purpose of the Study:
- To identify cellular genes and pathways essential for CVB and PV infection of human brain microvascular endothelial cells (BMECs).
- To compare the host cell requirements for CVB and PV at the BBB in vitro model.
Main Methods:
- Utilized a comparative RNA interference (RNAi) screening approach in an in vitro BBB model using human BMECs.
- Identified 117 genes influencing CVB and PV infection through RNAi screens.
Main Results:
- Depletion of 17 out of 22 genes broadly inhibited enterovirus infection, suggesting general antiviral roles.
- 46 out of 95 genes were required for both CVB and PV infection, including cell signaling components like adenylate cyclases.
- Specific gene requirements were observed for CVB or PV, involving Rab GTPases, Src tyrosine kinases, and tyrosine phosphatases.
Conclusions:
- Enteroviruses hijack specific cellular pathways within the BBB endothelium for entry and replication.
- These findings elucidate the molecular interactions between enteroviruses and the BBB endothelium, a key site for CNS viral infections.
- The identified genes and pathways represent potential targets for antiviral therapies against enteroviral meningitis.
