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Respiratory Syncytial Virus NS1 Protein Colocalizes with Mitochondrial Antiviral Signaling Protein MAVS following Infection

Overview of attention for article published in PLOS ONE, February 2012
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Title
Respiratory Syncytial Virus NS1 Protein Colocalizes with Mitochondrial Antiviral Signaling Protein MAVS following Infection
Published in
PLOS ONE, February 2012
DOI 10.1371/journal.pone.0029386
Pubmed ID
Authors

Sandhya Boyapalle, Terianne Wong, Julio Garay, Michael Teng, Homero San Juan-Vergara, Subhra Mohapatra, Shyam Mohapatra

Abstract

Respiratory syncytial virus (RSV) nonstructural protein 1(NS1) attenuates type-I interferon (IFN) production during RSV infection; however the precise role of RSV NS1 protein in orchestrating the early host-virus interaction during infection is poorly understood. Since NS1 constitutes the first RSV gene transcribed and the production of IFN depends upon RLR (RIG-I-like receptor) signaling, we reasoned that NS1 may interfere with this signaling. Herein, we report that NS1 is localized to mitochondria and binds to mitochondrial antiviral signaling protein (MAVS). Live-cell imaging of rgRSV-infected A549 human epithelial cells showed that RSV replication and transcription occurs in proximity to mitochondria. NS1 localization to mitochondria was directly visualized by confocal microscopy using a cell-permeable chemical probe for His(6)-NS1. Further, NS1 colocalization with MAVS in A549 cells infected with RSV was shown by confocal laser microscopy and immuno-electron microscopy. NS1 protein is present in the mitochondrial fraction and co-immunoprecipitates with MAVS in total cell lysatesof A549 cells transfected with the plasmid pNS1-Flag. By immunoprecipitation with anti-RIG-I antibody, RSV NS1 was shown to associate with MAVS at an early stage of RSV infection, and to disrupt MAVS interaction with RIG-I (retinoic acid inducible gene) and the downstream IFN antiviral and inflammatory response. Together, these results demonstrate that NS1 binds to MAVS and that this binding inhibits the MAVS-RIG-I interaction required for IFN production.

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Geographical breakdown

Country Count As %
United States 3 3%
Switzerland 1 <1%
Unknown 101 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 31 30%
Student > Bachelor 19 18%
Researcher 17 16%
Student > Master 7 7%
Student > Doctoral Student 5 5%
Other 10 10%
Unknown 16 15%
Readers by discipline Count As %
Agricultural and Biological Sciences 39 37%
Biochemistry, Genetics and Molecular Biology 18 17%
Immunology and Microbiology 16 15%
Medicine and Dentistry 7 7%
Engineering 2 2%
Other 5 5%
Unknown 18 17%