BPIFB3 Regulates Autophagy and Coxsackievirus B Replication through a Noncanonical Pathway Independent of the Core Initiation Machinery

Delorme-Axford E, Morosky S, Bomberger J, Stolz DB, Jackson WT, Coyne CB.

mBio. 2014; 9;5(6): e02147

Speaker: Yu-Lun Chen (陳昱倫)                                  Time: 14:00~15:00, Jun.24, 2015

Commentator: Dr. Shun-Hua Chen (陳舜華老師)       Place: Room 601

Abstract:

        Coxsackie virus B (CVB), a nonenveloped positive-sense ssRNA virus, belongs to picornaviridae and genus enterovirus. During infection, CVB induces a cellular pathway, termed autophagy, to provide the membranes necessary for its replication. In previous study, the authors have identified bactericidal/permeability-increasing protein fold-containing family B, member 3 (BPIFB3) byRNAi screening as a gene whose depletion significantly enhanced the replication of CVB in human brain microvascular endothelial cells (HBMEC). (Coyne et al., 2011) Here, the authors clarified the effect of BPIFB3 on CVB-induced autophagy pathway. The authors used BPIFB3 siRNA to silence BPIFB3 and established a C-terminal Flag fusion BPIFB3 construct to overexpress BPIFB3. The morphology of autophagy was observed by electron microscopy (EM). The autophagy components and BPIFB3 location were detected by immunofluorescence (IF) assay. Their findings showed that BPIFB3 was associated with the endoplasmic reticulum (ER), and its silencing enhanced basal levels of autophagy and promoted autophagy during CVB replication. Conversely, overexpression of BPIFB3 inhibited CVB replication and autophagy formation, and altered the morphology of LC3-positive vesicles. In addition, the authors found that silencing of core autophagy initiation components (Beclin-1, Atg14, UVRAG ) had no effect on CVB-induced autophagy or viral replication in cells transfected with BPIFB3 siRNA. In summary, this study reveal an uncharacterized regulator of CVB which controls replication through a noncanonical pathway.

Reference:

1.     Coyne, C.B., Bozym, R., Morosky, S.A., Hanna, S.L., Mukherjee, A., Tudor, M., Kim, K.S., and Cherry, S. (2011). Comparative RNAi screening reveals host factors involved in enterovirus infection of polarized endothelial monolayers. Cell host & microbe 9, 70-82.