Comparative RNAi Screening Reveals Host Factors Involved in Enterovirus Infection of Polarized Endothelial Monolayers
| Autor: | Carolyn B. Coyne, Amitava Mukherjee, Matthew Tudor, Rebecca A. Bozym, Kwang Sik Kim, Stefanie A. Morosky, Sheri L. Hanna, Sara Cherry |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Coxsackievirus medicine.disease_cause Microbiology Models Biological Article 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation RNA interference Virology Immunology and Microbiology(all) medicine Gene silencing Humans Mass Screening Gene Silencing Molecular Biology Mass screening 030304 developmental biology 0303 health sciences biology Endothelial Cells biology.organism_classification 3. Good health Enterovirus B Human Poliovirus Blood-Brain Barrier Host-Pathogen Interactions Enterovirus Parasitology Rab 030217 neurology & neurosurgery Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Cell Host & Microbe. 9(1):70-82 |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2011.01.001 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|