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PLoS One. 2015 Mar 3;10(3):e0117963. doi: 10.1371/journal.pone.0117963. eCollection 2015.

Proteomic analysis of mitochondrial-associated ER membranes (MAM) during RNA virus infection reveals dynamic changes in protein and organelle trafficking.

Author information

1
Department of Immunology, University of Washington, Seattle, Washington, United States of America; Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
2
Department of Immunology, University of Washington, Seattle, Washington, United States of America.
3
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.

Abstract

RIG-I pathway signaling of innate immunity against RNA virus infection is organized between the ER and mitochondria on a subdomain of the ER called the mitochondrial-associated ER membrane (MAM). The RIG-I adaptor protein MAVS transmits downstream signaling of antiviral immunity, with signaling complexes assembling on the MAM in association with mitochondria and peroxisomes. To identify components that regulate MAVS signalosome assembly on the MAM, we characterized the proteome of MAM, ER, and cytosol from cells infected with either chronic (hepatitis C) or acute (Sendai) RNA virus infections, as well as mock-infected cells. Comparative analysis of protein trafficking dynamics during both chronic and acute viral infection reveals differential protein profiles in the MAM during RIG-I pathway activation. We identified proteins and biochemical pathways recruited into and out of the MAM in both chronic and acute RNA viral infections, representing proteins that drive immunity and/or regulate viral replication. In addition, by using this comparative proteomics approach, we identified 3 new MAVS-interacting proteins, RAB1B, VTN, and LONP1, and defined LONP1 as a positive regulator of the RIG-I pathway. Our proteomic analysis also reveals a dynamic cross-talk between subcellular compartments during both acute and chronic RNA virus infection, and demonstrates the importance of the MAM as a central platform that coordinates innate immune signaling to initiate immunity against RNA virus infection.

PMID:
25734423
PMCID:
PMC4348417
DOI:
10.1371/journal.pone.0117963
[Indexed for MEDLINE]
Free PMC Article
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