Standing on three legs: antiviral activities of RIG-I against influenza viruses

Weber-Gerlach, Michaela; Weber, Friedemann

doi:10.1016/j.coi.2016.05.016

Cited by 46 publications

(44 citation statements)

References 51 publications

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“…It has been reported that PACT is a crucial antiviral host factor that mediates the activation of the dsRNA-dependent kinase PKR, and stimulates substantial RIG-I activation to induce IFN-I production 47 . When PACT was co-expressed with RIG-I, the IFNβ promoter activity induced by IAV RNP complex was most robust 48 .…”

Section: Discussionmentioning

confidence: 99%

Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication

Guo

Bao

et al. 2020

Sci Rep

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Epidemic and pandemic influenza A virus (IAV) poses a significant threat to human populations worldwide. Iridoid glycosides are principal bioactive components from the Gardenia jasminoides J. Ellis fruit that exhibit antiviral activity against several strains of IAV. In the present study, we evaluated the protective effect of Fructus Gardeniae iridoid glycoside extracts (IGEs) against IAV by cytopathogenic effect(CPE), MTT and a plaque formation assay in vitro and examined the reduction in the pulmonary index (PI), restoration of body weight, reduction in mortality and increases in survival time in vivo.As a host factor, PACT provides protection against the pathogenic influenza A virus by interacting with IAV polymerase and activating the IFN-I response. To verify the whether IGEs suppress IAV replication in a PACT-dependent manner, IAV RNA replication, expression of PACT and the phosphorylation of eIF2α in A549 cells were detected; the levels of IFNβ, PACT and PKR in mouse lung tissues were determined; and the activity of IAV polymerase was evaluated in PACT-compromised cells. The results indicated that IGEs sufficiently alleviated cell damage and suppressed IAV replication in vitro, protecting mice from IAV-induced injury and lethal IAV infection. These anti-IAV effects might be related to disrupted interplay between IVA polymerase and PACT and/or prevention of a PACT-dependent overactivated IFN-I antiviral response. Taken together, our findings reveal a new facet of the mechanisms by which IGEs fight the influenza A virus in a PACT-dependent manner.

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Section: Discussionmentioning

confidence: 99%

Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication

Guo

Bao

et al. 2020

Sci Rep

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“…Part of the potent antitumor activity of RIG-I ligands is its ability to promote crosspresentation of antigens to CD8 T cells and to induce cytotoxic activity (Hochheiser et al, 2016). RIG-I ligands show strong therapeutic activity in viral infection models such as influenza (Weber-Gerlach & Weber, 2016). Notably, RIG-I has also been shown to be involved in the detection of intracellular bacteria (Abdullah et al, 2012).…”

Section: Rig-imentioning

confidence: 99%

Nucleic Acid Immunity

Hartmann

2017

Advances in Immunology

204

169

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Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to advance medicine.

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“…Cell type-dependent antigen handling based on interactions with lectin, complement and Fc receptors on different subsets of antigen presenting cells (105–109) might also lead to differences in the specificity or functionality of CD4 T cells specific for cytoplasmic, non-glycosylated internal virion proteins compared to membrane glycoproteins. Also, the presence of viral RNA associated with ribonucleoprotein, acting as TLR ligands (110–112), could change the activation state of the antigen presenting cell and thus the functionality of the CD4 T cells elicited. Finally, whether or not a viral antigen is available only after the highly inflammatory environment of infection (NS1) or is also abundant in vaccines delivered as an intramuscular injection (e.g.…”

Section: The Role Of Viral Antigen Specificity In Protective Immunitymentioning

confidence: 99%

CD4 T cells in protection from influenza virus: Viral antigen specificity and functional potential

Sant

DiPiazza

Nayak

et al. 2018

Immunological Reviews

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CD4 T cells convey a number of discrete functions to protective immunity to influenza, a complexity that distinguishes this arm of adaptive immunity from B cells and CD8 T cells. Although the most well recognized function of CD4 T cells is provision of help for antibody production, CD4 T cells are important in many aspects of protective immunity. Our studies have revealed that viral antigen specificity is a key determinant of CD4 T cell function, as illustrated both by mouse models of infection and human vaccine responses, a factor whose importance is due at least in part to events in viral antigen handling. We discuss research that has provided insight into the diverse viral epitope specificity of CD4 T cells elicited after infection, how this primary response is modified as CD4 T cells home to the lung, establish memory, and after challenge with a secondary and distinct influenza virus strain. Our studies in human subjects point out the challenges facing vaccine efforts to facilitate responses to novel and avian strains of influenza, as well as strategies that enhance the ability of CD4 T cells to promote protective antibody responses to both seasonal and potentially pandemic strains of influenza.

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Standing on three legs: antiviral activities of RIG-I against influenza viruses

Cited by 46 publications

References 51 publications

Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication

Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication

Nucleic Acid Immunity

CD4 T cells in protection from influenza virus: Viral antigen specificity and functional potential

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