Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Y RNAs are conserved endogenous RIG-I ligands across RNA virus infection and are targeted by HIV-1

ABSTRACT: Pattern recognition receptors (PRRs) protect against microbial invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. While microbial-derived PRR ligands have been extensively characterized, the contribution and relevance of endogenous ligands to PRR activation remains overlooked. Here, we characterize the landscape of endogenous ligands that engage RIG-I-like receptors (RLRs) upon infection by different RNA viruses. In each infection, several RNAs transcribed by RNA polymerase III (Pol3) specifically engaged RLRs, particularly the family of Y RNAs. Sensing of Y RNAs was dependent on their mimicking of viral secondary structure and their 5’-triphosphate extremity. Further, we found that HIV-1 triggered a VPR-dependent downregulation of RNA triphosphatase DUSP11 in vitro and in vivo, inducing a transcriptome-wide change of cellular RNA 5’-triphosphorylation that licenses Y RNA immunogenicity. Overall, our work uncovers the contribution of endogenous RNAs to antiviral immunity and demonstrates the importance of this pathway in HIV-1 infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE203128 | GEO | 2022/05/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Viral Mimicry by Endogenous Y-RNAs Contributes to Antiviral Immunity [mock]

Project description:Pattern recognition receptors (PRRs) protect against host invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. While microbial-derived PRR ligands have been extensively characterized, the contribution and relevance of endogenous ligands to PRR activation during viral infection remain overlooked. In this work, we characterize the landscape of endogenous ligands that engage RIG-I-like receptors upon infection by a positive-sense RNA virus, a negative-sense RNA virus or a retrovirus. We found that several endogenous RNAs transcribed by RNA polymerase 3 (Pol3), and in particular the Y-RNA family of small non-coding repeats, bind and activate RIG-I. We show that this recognition is dependent on Y-RNA mimicking viral secondary structure and its 5’-triphosphate extremity. Further, we found that HIV-1 infection triggers a VPR-dependent downregulation of RNA triphosphatase DUSP11 in vitro and in vivo, leading to an increase of Y-RNA 5’-triphosphorylation that enables their immunogenicity. Importantly, we show that altering DUSP11 expression is sufficient to induce a type-I interferon and T cell activation transcriptional program associated with HIV-1 infection. Overall, our work uncovers the critical contribution of endogenous RNAs ligands to antiviral immunity and demonstrates the role of this pathway in HIV-1 infection.

2022-04-29 | GSE134860 | GEO

Viral Mimicry by Endogenous Y-RNAs Contributes to Antiviral Immunity [DV-4]

2022-04-29 | GSE134856 | GEO

Viral Mimicry by Endogenous Y-RNAs Contributes to Antiviral Immunity [MVseq2]

2022-08-01 | GSE134859 | GEO

Viral Mimicry by Endogenous Y-RNAs Contributes to Antiviral Immunity [MV]

2022-04-29 | GSE134858 | GEO

Viral Mimicry by Endogenous Y-RNAs Contributes to Antiviral Immunity [HIV]

2022-04-29 | GSE134857 | GEO

Y RNAs are conserved endogenous RIG-I ligands across RNA virus infection and are targeted by HIV-1

Project description:Y RNAs are conserved endogenous RIG-I ligands across RNA virus infection and are targeted by HIV-1

| PRJNA838613 | ENA

ACTG A5258 Clinical administration of chloroquine to HIV-infected patients receiving antiretroviral therapy to reduce immune activation

Project description:ACTG A5258, we asked whether chloroquine could reduce the immune activation in HIV infection posited to be driven by microbial TLR agonists, such as bacterial elements translocated from the gut and HIV-1 RNAs . We anticipate that blocking this activation pathway might interfere with events in pathogenesis leading to AIDS- and non-AIDS-related clinical manifestations of HIV disease.

2016-07-15 | GSE71064 | GEO

ACTG A5258 Clinical administration of chloroquine to patients with untreated chronic HIV infection to reduce immune activation

2016-07-15 | GSE71063 | GEO

An adjuvant strategy enabled by modulation of the physical properties of fungal ligands expands viral glycoprotein immunogenicity

Project description:Activation of the innate immune system via pattern recognition receptors (PRRs) is key to generate lasting adaptive immunity. PRRs detect unique chemical patterns associated with invading microorganism, but if and how the physical properties of PRR ligands influence development of the immune response remains unknown. Through the study of fungal mannans we show that the physical form of PRR ligands dictates the immune response. Soluble mannans are immunosilent in the periphery but elicit a potent pro-inflammatory response in the draining lymph node (dLN). By modulating the physical form of mannans, we developed a formulation that targets both the periphery and dLN. When combined with viral glycoprotein antigens, this mannan formulation broadens epitope recognition, elicits potent antigen-specific neutralizing antibodies, and confers protection against viral infections of the lung. Thus, the physical properties of microbial ligands determine the outcome of the immune response and can be harnessed for vaccine development.

2022-01-13 | GSE193419 | GEO

ACTG A5258 Clinical administration of chloroquine to patients with untreated chronic HIV infection to reduce immune activation

2016-07-15 | E-GEOD-71063 | biostudies-arrayexpress