tetano
Editor, Senior Moderator
First Published on July 27, 2014, doi: 10.1074/jbc.M114.558817 jbc.M114.558817.
Phospholipase D facilitates efficient entry of influenza virus allowing escape from innate mmune inhibition
Thomas H. Oguin III1,
Shalini Sharma2,
Amanda D. Stuart3,
Susu Duan4,
Sarah A. Scott5,
Carrie K. Jones5,
J. Scott Daniels5,
Craig W. Lindsley5,
Paul G. Thomas4 and
H. Alex Brown6*
+ Author Affiliations
1 St Jude Children's Research Hospital, United States;
2 Lala Lajpat Rai University of Veterinary and A, India;
3 University of Cambridge, United Kingdom;
4 St Jude Childrens Research Hospital, United States;
5 Vanderbilt University, United States;
6 Vanderbilt.University, United States
↵* Corresponding author; email: alex.brown@vanderbilt.edu
Capsule
Background: Identifying host factors used by influenza can aid in the defense against pandemics that threaten public health.
Results: Phospholipase D (PLD) contributes to viral infection and innate immune evasion strategies.
Conclusion: Inhibition of PLD activity reduces influenza reproduction.
Significance: PLD inhibition presents a novel approach to restrict influenza infection and viral escape.
Abstract
Lipid metabolism plays a fundamental role during influenza virus replication, although key regulators of lipid-dependent trafficking and virus production remain inadequately defined. This report demonstrates that infection by influenza virus stimulates phospholipase D (PLD) activity and PLD co-localizes with influenza during infection. Both chemical inhibition and RNA interference of PLD delayed viral entry and reduced viral titers in vitro. Although there may be contributions by both major isoenzymes, the effects on viral infectivity appear more dependent on the PLD2 isoenzyme. In vivo, PLD inhibition reduced virus titer and correlated with significant increases in transcription of innate antiviral effectors. In vitro the reduction in viral titer downstream of PLD2 inhibition was dependent on RIG-I, IRF3, and MxA, but not IRF7. Inhibition of PLD2 accelerated the accumulation of MxA in foci as early as 30 minutes post-infection. Together these data suggest that PLD facilitates the rapid endocytosis of influenza virus, permitting viral escape from innate immune detection and effectors that are capable of limiting lethal infection.
full article
http://www.jbc.org/content/early/2014/07/27/jbc.M114.558817.full.pdf+html
Phospholipase D facilitates efficient entry of influenza virus allowing escape from innate mmune inhibition
Thomas H. Oguin III1,
Shalini Sharma2,
Amanda D. Stuart3,
Susu Duan4,
Sarah A. Scott5,
Carrie K. Jones5,
J. Scott Daniels5,
Craig W. Lindsley5,
Paul G. Thomas4 and
H. Alex Brown6*
+ Author Affiliations
1 St Jude Children's Research Hospital, United States;
2 Lala Lajpat Rai University of Veterinary and A, India;
3 University of Cambridge, United Kingdom;
4 St Jude Childrens Research Hospital, United States;
5 Vanderbilt University, United States;
6 Vanderbilt.University, United States
↵* Corresponding author; email: alex.brown@vanderbilt.edu
Capsule
Background: Identifying host factors used by influenza can aid in the defense against pandemics that threaten public health.
Results: Phospholipase D (PLD) contributes to viral infection and innate immune evasion strategies.
Conclusion: Inhibition of PLD activity reduces influenza reproduction.
Significance: PLD inhibition presents a novel approach to restrict influenza infection and viral escape.
Abstract
Lipid metabolism plays a fundamental role during influenza virus replication, although key regulators of lipid-dependent trafficking and virus production remain inadequately defined. This report demonstrates that infection by influenza virus stimulates phospholipase D (PLD) activity and PLD co-localizes with influenza during infection. Both chemical inhibition and RNA interference of PLD delayed viral entry and reduced viral titers in vitro. Although there may be contributions by both major isoenzymes, the effects on viral infectivity appear more dependent on the PLD2 isoenzyme. In vivo, PLD inhibition reduced virus titer and correlated with significant increases in transcription of innate antiviral effectors. In vitro the reduction in viral titer downstream of PLD2 inhibition was dependent on RIG-I, IRF3, and MxA, but not IRF7. Inhibition of PLD2 accelerated the accumulation of MxA in foci as early as 30 minutes post-infection. Together these data suggest that PLD facilitates the rapid endocytosis of influenza virus, permitting viral escape from innate immune detection and effectors that are capable of limiting lethal infection.
full article
http://www.jbc.org/content/early/2014/07/27/jbc.M114.558817.full.pdf+html