Comparative RNAi screening reveals host factors involved in enterovirus infection of polarized endothelial monolayers.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Coyne, CB; Bozym, R; Morosky, SA; Hanna, SL; Mukherjee, A; Tudor, M; Kim, KS; Cherry, S

Published Date

  • January 20, 2011

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 70 - 82

PubMed ID

  • 21238948

Pubmed Central ID

  • PMC3048761

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2011.01.001

Language

  • eng

Conference Location

  • United States