Dataset Information

Structural Variability in the RLR-MAVS Pathway and Sensitive Detection of Viral RNAs.

ABSTRACT: Cells need high-sensitivity detection of non-self molecules in order to fight against pathogens. These cellular sensors are thus of significant importance to medicinal purposes, especially for treating novel emerging pathogens. RIG-I-like receptors (RLRs) are intracellular sensors for viral RNAs (vRNAs). Their active forms activate mitochondrial antiviral signaling protein (MAVS) and trigger downstream immune responses against viral infection. Functional and structural studies of the RLR-MAVS signaling pathway have revealed significant supramolecular variability in the past few years, which revealed different aspects of the functional signaling pathway. Here I will discuss the molecular events of RLR-MAVS pathway from the angle of detecting single copy or a very low copy number of vRNAs in the presence of non-specific competition from cytosolic RNAs, and review key structural variability in the RLR / vRNA complexes, the MAVS helical polymers, and the adapter-mediated interactions between the active RLR / vRNA complex and the inactive MAVS in triggering the initiation of the MAVS filaments. These structural variations may not be exclusive to each other, but instead may reflect the adaptation of the signaling pathways to different conditions or reach different levels of sensitivity in its response to exogenous vRNAs.

SUBMITTER: Jiang QX

PROVIDER: S-EPMC6858087 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Structural Variability in the RLR-MAVS Pathway and Sensitive Detection of Viral RNAs.

Jiang Qiu-Xing QX

Medicinal chemistry (Shariqah (United Arab Emirates)) 20190101 5

Cells need high-sensitivity detection of non-self molecules in order to fight against pathogens. These cellular sensors are thus of significant importance to medicinal purposes, especially for treating novel emerging pathogens. RIG-I-like receptors (RLRs) are intracellular sensors for viral RNAs (vRNAs). Their active forms activate mitochondrial antiviral signaling protein (MAVS) and trigger downstream immune responses against viral infection. Functional and structural studies of the RLR-MAVS si ...[more]

PMID: 30569868

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Project description:The family Arenaviridae includes several important human pathogens that can cause severe hemorrhagic fever and greatly threaten public health. As a major component of the innate immune system, the RLR/MAVS signaling pathway is involved in recognizing viral components and initiating antiviral activity. It has been reported that arenavirus infection can suppress the innate immune response, and NP and Z proteins of pathogenic arenaviruses can disrupt RLR/MAVS signaling, thus inhibiting production of type I interferon (IFN-I). However, recent studies have shown elevated IFN-I levels in certain arenavirus-infected cells. The mechanism by which arenavirus infection induces IFN-I responses remains unclear. In this study, we determined that the L polymerase (Lp) of Mopeia virus (MOPV), an Old World (OW) arenavirus, can activate the RLR/MAVS pathway and thus induce the production of IFN-I. This activation is associated with the RNA-dependent RNA polymerase activity of Lp. This study provides a foundation for further studies of interactions between arenaviruses and the innate immune system and for the elucidation of arenavirus pathogenesis. IMPORTANCE:Distinct innate immune responses are observed when hosts are infected with different arenaviruses. It has been widely accepted that NP and certain Z proteins of arenaviruses inhibit the RLR/MAVS signaling pathway. The viral components responsible for the activation of the RLR/MAVS signaling pathway remain to be determined. In the current study, we demonstrate for the first time that the Lp of MOPV, an OW arenavirus, can activate the RLR/MAVS signaling pathway and thus induce the production of IFN-I. Based on our results, we proposed that dynamic interactions exist among Lp-produced RNA, NP, and the RLR/MAVS signaling pathway, and the outcome of these interactions may determine the final IFN-I response pattern: elevated or reduced. Our study provides a possible explanation for how IFN-I can become activated during arenavirus infection and may help us gain insights into the interactions that form between different arenavirus components and the innate immune system.

Dataset Information

Structural Variability in the RLR-MAVS Pathway and Sensitive Detection of Viral RNAs.

Publications

Structural Variability in the RLR-MAVS Pathway and Sensitive Detection of Viral RNAs.

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