tetano
Editor, Senior Moderator
J Virol. 2013 Oct 23. [Epub ahead of print]
PLC-γ1 signaling plays a subtype-specific role in post-binding cell entry of Influenza A virus.
Zhu L, Ly H, Liang Y.
Source
Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, MN 55108. USA.
Abstract
Host signaling pathways and cellular proteins play important roles in the influenza viral life cycle and can serve as antiviral targets. In this study we report the engagement of host phosphoinositide-specific phospholipase γ1 (PLC-γ1) in mediating cell entry of influenza virus H1N1 but not H3N2 subtype. Both PLC-γ1-specific inhibitor and shRNA strongly suppress the replication of H1N1 but not H3N2 viruses in cell culture, suggesting that PLC-γ1 plays an important subtype-specific role in the influenza viral life cycle. Further analyses demonstrate that PLC-γ1 activation is required for viral post-binding cell entry. In addition, H1N1 but not H3N2 infection leads to the phosphorylation of PLC-γ1 at Ser 1248 immediately after infection and independent of viral replication. We have further shown that H1N1-induced PLC-γ1 activation is downstream of epidermal growth factor receptor (EGFR) signaling. Interestingly, both H1N1 and H3N2 infections activate EGFR, but only H1N1 leads to PLC-γ1 activation. Taken together, we have identified for the first time the subtype-specific interplay of host PLC-γ1 signaling and H1N1 virus that is critical for viral uptake early in the infection. Our study provides novel insights into how virus interacts with cellular signaling network by demonstrating that viral determinants can regulate how the host signaling pathways function in virally infected cells.
PMID:
24155396
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24155396
PLC-γ1 signaling plays a subtype-specific role in post-binding cell entry of Influenza A virus.
Zhu L, Ly H, Liang Y.
Source
Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, MN 55108. USA.
Abstract
Host signaling pathways and cellular proteins play important roles in the influenza viral life cycle and can serve as antiviral targets. In this study we report the engagement of host phosphoinositide-specific phospholipase γ1 (PLC-γ1) in mediating cell entry of influenza virus H1N1 but not H3N2 subtype. Both PLC-γ1-specific inhibitor and shRNA strongly suppress the replication of H1N1 but not H3N2 viruses in cell culture, suggesting that PLC-γ1 plays an important subtype-specific role in the influenza viral life cycle. Further analyses demonstrate that PLC-γ1 activation is required for viral post-binding cell entry. In addition, H1N1 but not H3N2 infection leads to the phosphorylation of PLC-γ1 at Ser 1248 immediately after infection and independent of viral replication. We have further shown that H1N1-induced PLC-γ1 activation is downstream of epidermal growth factor receptor (EGFR) signaling. Interestingly, both H1N1 and H3N2 infections activate EGFR, but only H1N1 leads to PLC-γ1 activation. Taken together, we have identified for the first time the subtype-specific interplay of host PLC-γ1 signaling and H1N1 virus that is critical for viral uptake early in the infection. Our study provides novel insights into how virus interacts with cellular signaling network by demonstrating that viral determinants can regulate how the host signaling pathways function in virally infected cells.
PMID:
24155396
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24155396