tetano
Editor, Senior Moderator
Nat Commun. 2013 Nov 14;4:2763. doi: 10.1038/ncomms3763.
A Ca(2+)-dependent signalling circuit regulates influenza A virus internalization and infection.
Fujioka Y1, Tsuda M2, Nanbo A1, Hattori T3, Sasaki J4, Sasaki T4, Miyazaki T5, Ohba Y1.
Author information
Abstract
Various viruses enter host cells via endocytosis, but the molecular mechanisms underlying the specific internalization pathways remain unclear. Here we show that influenza A viruses (IAVs) enter cells via redundant pathways of clathrin-mediated and clathrin-independent endocytosis, with intracellular Ca(2+) having a central role in regulation of both pathways by activating a signalling axis comprising RhoA, Rho-kinase, phosphatidylinositol 4-phosphate 5-kinase (PIP5K) and phospholipase C (PLC). IAV infection induces oscillations in the cytosolic Ca(2+) concentration of host cells, the prevention of which markedly attenuates virus internalization and infection. The small GTPase RhoA is found both to function downstream of the virus-induced Ca(2+) response and itself to induce Ca(2+) oscillations in a manner dependent on Rho-kinase and subsequent PIP5K-PLC signalling. This signalling circuit regulates both clathrin-mediated and clathrin-independent endocytosis during virus infection and seems to constitute a key mechanism for regulation of IAV internalization and infection.
PMID:
24434940
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/24434940
A Ca(2+)-dependent signalling circuit regulates influenza A virus internalization and infection.
Fujioka Y1, Tsuda M2, Nanbo A1, Hattori T3, Sasaki J4, Sasaki T4, Miyazaki T5, Ohba Y1.
Author information
Abstract
Various viruses enter host cells via endocytosis, but the molecular mechanisms underlying the specific internalization pathways remain unclear. Here we show that influenza A viruses (IAVs) enter cells via redundant pathways of clathrin-mediated and clathrin-independent endocytosis, with intracellular Ca(2+) having a central role in regulation of both pathways by activating a signalling axis comprising RhoA, Rho-kinase, phosphatidylinositol 4-phosphate 5-kinase (PIP5K) and phospholipase C (PLC). IAV infection induces oscillations in the cytosolic Ca(2+) concentration of host cells, the prevention of which markedly attenuates virus internalization and infection. The small GTPase RhoA is found both to function downstream of the virus-induced Ca(2+) response and itself to induce Ca(2+) oscillations in a manner dependent on Rho-kinase and subsequent PIP5K-PLC signalling. This signalling circuit regulates both clathrin-mediated and clathrin-independent endocytosis during virus infection and seems to constitute a key mechanism for regulation of IAV internalization and infection.
PMID:
24434940
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/24434940