TY - JOUR
T1 - Comparative RNAi screening reveals host factors involved in enterovirus infection of polarized endothelial monolayers
AU - Coyne, Carolyn B.
AU - Bozym, Rebecca
AU - Morosky, Stefanie A.
AU - Hanna, Sheri L.
AU - Mukherjee, Amitava
AU - Tudor, Matthew
AU - Kim, Kwang Sik
AU - Cherry, Sara
N1 - Funding Information:
We are grateful to those who have generously shared reagents. We thank the Penn Cell Based Screening Core for technical assistance, and Robert Doms for careful review of the manuscript. This work was supported by grants from the National Institutes of Health (R01AI081759 [CBC] and R01AI074951, U54AI057168 [SC]).
PY - 2011/1/20
Y1 - 2011/1/20
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chom.2011.01.001
DO - 10.1016/j.chom.2011.01.001
M3 - Article
C2 - 21238948
AN - SCOPUS:78751484574
SN - 1931-3128
VL - 9
SP - 70
EP - 82
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 1
ER -