Present address: Department of Infectious Diseases, Molecular Virology, University of Heidelberg, D-69120 Heidelberg, Germany.
Cell permeabilization by poliovirus 2B viroporin triggers bystander permeabilization in neighbouring cells through a mechanism involving gap junctions
Article first published online: 12 MAR 2010
© 2010 Blackwell Publishing Ltd
Volume 12, Issue 8, pages 1144–1157, August 2010
How to Cite
Madan, V., Redondo, N. and Carrasco, L. (2010), Cell permeabilization by poliovirus 2B viroporin triggers bystander permeabilization in neighbouring cells through a mechanism involving gap junctions. Cellular Microbiology, 12: 1144–1157. doi: 10.1111/j.1462-5822.2010.01460.x
- Issue published online: 9 JUL 2010
- Article first published online: 12 MAR 2010
- Received 22 November, 2009; revised 21 February, 2010; accepted 10 March, 2010.
Poliovirus 2B protein is a well-known viroporin implicated in plasma membrane permeabilization to ions and low-molecular-weight compounds during infection. Translation in mammalian cells expressing 2B protein is inhibited by hygromycin B (HB) but remains unaffected in mock cells, which are not permeable to the inhibitor. Here we describe a previously unreported bystander effect in which healthy baby hamster kidney (BHK) cells become sensitive to HB when co-cultured with a low proportion of cells expressing poliovirus 2B. Viroporins E from mouse hepatitis virus, 6K from Sindbis virus and NS4A protein from hepatitis C virus were also able to permeabilize neighbouring cells to different extents. Expression of 2B induced permeabilization of neighbouring cell lines other than BHK. We found that gap junctions are responsible mediating the observed bystander permeabilization. Gap junctional communication was confirmed in 2B-expressing co-cultures by fluorescent dye transfer. Moreover, the presence of connexin 43 was confirmed in both mock and 2B-transfected cells. Finally, inhibition of HB entry to neighbouring cells was observed with 18α-glycyrrhethinic acid, an inhibitor of gap junctions. Taken together, these findings support a mechanism involving gap junctional intercellular communication in the bystander permeabilization effect observed in healthy cells co-cultured with poliovirus 2B-expressing cells.