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Regulation of RIG-I-like receptor signaling by host and viral proteins

https://doi.org/10.1016/j.cytogfr.2014.06.005Get rights and content

Abstract

Vertebrate innate immunity is characterized by an effective immune surveillance apparatus, evolved to sense foreign structures, such as proteins or nucleic acids of invading microbes. RIG-I-like receptors (RLRs) are key sensors of viral RNA species in the host cell cytoplasm. Activation of RLRs in response to viral RNA triggers an antiviral defense program through the production of hundreds of antiviral effector proteins including cytokines, chemokines, and host restriction factors that directly interfere with distinct steps in the virus life cycle. To avoid premature or abnormal antiviral and proinflammatory responses, which could have harmful consequences for the host, the signaling activities of RLRs and their common adaptor molecule, MAVS, are delicately controlled by cell-intrinsic regulatory mechanisms. Furthermore, viruses have evolved multiple strategies to modulate RLR-MAVS signal transduction to escape from immune surveillance. Here, we summarize recent progress in our understanding of the regulation of RLR signaling through host factors and viral antagonistic proteins.

Keywords

Innate immunity
Type-I interferon
RIG-I
MDA5
Viral immune evasion

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Jessica Chiang is a Ph.D. candidate in the Virology Graduate Program at Harvard Medical School, Boston. She completed her B.S. in Molecular, Cell, and Developmental Biology at the University of California, Los Angeles. Her research interests include virus entry mechanisms and the strategies employed by RNA and DNA viruses to evade innate immunity. Her previous work focused on the development and characterization of entry inhibitors of HIV-1. Her current research, conducted in the Gack laboratory, is focused on innate immune sensing mechanisms of DNA viruses as well as the strategies used by DNA viruses to escape the type-I interferon-mediated innate immune response.

Meredith Davis graduated with a B.S. in Biochemistry from the University of Missouri-Columbia and is currently a Ph.D. candidate in Virology at Harvard Medical School. Her broad interest in virology includes host–virus interactions and the mechanisms by which viruses usurp or evade critical cellular pathways for their efficient replication. During her undergraduate studies, her research focused on the mechanisms of how viruses utilize the DNA damage response for their own benefit. Since joining the Gack laboratory in 2011, her research has focused on deciphering the mechanisms of how paramyxovirus family members evade antiviral signaling initiated by RIG-I-like receptors. During her thesis research, she identified a novel mechanism utilized by measles and Nipah virus to antagonize innate immune activation by MDA5 through targeting the phosphatases PP1α and PP1γ.

Michaela Gack is an Assistant Professor in the Department of Microbiology and Immunobiology at Harvard Medical School, Boston. Dr. Gack received her Ph.D. degree in Molecular Virology from the collaborative graduate training program between Harvard Medical School and the Friedrich Alexander University Erlangen-Nuremberg, Germany. She completed her postdoctoral training at the University of Southern California. Dr. Gack's research seeks a better understanding of the molecular mechanisms underlying innate immune sensing of RNA viruses and the subsequent type-I interferon response to limit virus replication. Using a combination of proteomics and biochemical, molecular, and cell biological approaches, her laboratory is identifying and characterizing the regulatory mechanisms of RIG-I-like receptor signaling through host factors. Her research interests also include mechanisms of viral evasion as well as the role of TRIM proteins in antiviral defenses. For her academic achievements in the fields of innate immunity and virology, Dr. Gack received several awards including the 2009 GE & Science Prize for Young Life Scientists, the 2013 Junior Investigator Award from the European Society for Virology, and the Ann Palmenberg Junior Investigator Award 2013 from the American Society for Virology. Furthermore, Dr. Gack was awarded with the 2014 Merck Irving S. Sigal Memorial Award from the American Society for Microbiology. Since 2012, Dr. Gack has been an Associate Editor for the journal PLoS Pathogens.

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These authors contributed equally.

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