MOV10 Provides Antiviral Activity against RNA Viruses by Enhancing RIG-I–MAVS-Independent IFN Induction

Cuevas, Rolando; Ghosh, Arundhati; Wallerath, Christina; Hornung, Veit; Coyne, Carolyn B.; Sarkar, Saumendra N.

doi:10.4049/jimmunol.1501359

Cited by 60 publications

(65 citation statements)

References 43 publications

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“…Notably, many SARS-CoV-2 RNA interactome members are directly or indirectly linked to the IFN response. These include PUM1 43,44 , YBX1 44,45 , SYNCRIP 46 , G3BP1 [47][48][49][50] , G3BP2 47,48 , EIF4B 51 , MOV10 [52][53][54] , CAPRIN1 48 , DDX3X [55][56][57][58] , LSM14A 59,60 , RYDEN 61,62 , STRAP 63 , ANXA1 64,65 , DDX1 [66][67][68] , PCBP2 69,70 , HNRNPA2B1 71 , and YWHAZ 72 . In conclusion, our global protein abundance measurements verify the induction of an appropriate host response in SARS-CoV-2 infected HuH-7 cells and further support an essential role for IFN and MAPK signaling in SARS-CoV-2 infections.…”

Section: Biological Functions Of Human Sars-cov-2-bound Proteinsmentioning

confidence: 99%

A direct RNA-protein interaction atlas of the SARS-CoV-2 RNA in infected human cells

Schmidt

Lareau

Keshishian

et al. 2020

Preprint

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SARS-CoV-2 infections pose a global threat to human health and an unprecedented research challenge. Among the most urgent tasks is obtaining a detailed understanding of the molecular interactions that facilitate viral replication or contribute to host defense mechanisms in infected cells. While SARS-CoV-2 co-opts cellular factors for viral translation and genome replication, a comprehensive map of the host cell proteome in direct contact with viral RNA has not been elucidated. Here, we use RNA antisense purification and mass spectrometry (RAP-MS) to obtain an unbiased and quantitative picture of the human proteome that directly binds the SARS-CoV-2 RNA in infected human cells. We discover known host factors required for coronavirus replication, regulators of RNA metabolism and host defense pathways, along with dozens of potential drug targets among direct SARS-CoV-2 binders. We further integrate the SARS-CoV-2 RNA interactome with proteome dynamics induced by viral infection, linking interactome proteins to the emerging biology of SARS-CoV-2 infections. Validating RAP-MS, we show that CNBP, a regulator of proinflammatory cytokines, directly engages the SARS-CoV-2 RNA. Supporting the functional relevance of identified interactors, we show that the interferon-induced protein RYDEN suppresses SARS-CoV-2 ribosomal frameshifting and demonstrate that inhibition of SARS-CoV-2-bound proteins is sufficient to manipulate viral replication. The SARS-CoV-2 RNA interactome provides an unprecedented molecular perspective on SARS-CoV-2 infections and enables the systematic dissection of host dependency factors and host defense strategies, a crucial prerequisite for designing novel therapeutic strategies.

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Section: Biological Functions Of Human Sars-cov-2-bound Proteinsmentioning

confidence: 99%

A direct RNA-protein interaction atlas of the SARS-CoV-2 RNA in infected human cells

Schmidt

Lareau

Keshishian

et al. 2020

Preprint

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“…CRISPR-Cas9-mediated genome editing was carried out as described previously (24)(25)(26), with the use of murine IRF1 target sequence GAAGCACGCTGCTAAGCACGG. Briefly, plasmidencoding gRNA, Cas9-mCherry was transfected into MC38, CT26, and B16-F10 parental cell lines with lipofectamine 3000 (Thermo Fisher Scientific).…”

Section: Generating Irf1-deficient (Irf1-ko) and Pd-l1-expressing Celmentioning

confidence: 99%

IRF1 Inhibits Antitumor Immunity through the Upregulation of PD-L1 in the Tumor Cell

Shao

Hou

Scharping

et al. 2019

Cancer Immunology Research

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Multiple studies have associated the transcription factor IRF1 with tumor-suppressive activities. Here, we report an opposite tumor cell-intrinsic function of IRF1 in promoting tumor growth. IRF1-deficient tumor cells showed reduced tumor growth in MC38 and CT26 colon carcinoma and B16 melanoma mouse models. This reduction in tumor growth was dependent on host CD8 þ T cells. Detailed profiling of tumor-infiltrating leukocytes did not show changes in the various T-cell and myeloid cell populations. However, CD8 þ T cells that had infiltrated IRF1-deficieint tumors in vivo exhibited enhanced cytotoxicity. IRF1-deficient tumor cells lost the ability to upregulate PD-L1 expression in vitro and in vivo and were more susceptible to T-cell-mediated killing. Induced expression of PD-L1 in IRF1-deficient tumor cells restored tumor growth. These results indicate differential activity of IRF1 in tumor escape.

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“…The human ERI-6/7 homolog Mov10 is an antiviral factor and restricts retrotransposon activity (10, 11). Mov10 binds to 3’UTRs and is thought to clear these of 3’UTR binding proteins and/or secondary structures (12); Mov10 also has helicase-independent anti-viral activity(13). C. elegans harbors fragments and full-length copies of at least 20 families of LTR-containing retrotransposons that belong to the Ty3/gypsy and the BEL/Pao classes (14, 15).…”

Section: Introductionmentioning

confidence: 99%

Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons

Fischer

Ruvkun

2019

Preprint

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18Endogenous retroviruses and LTR retrotransposons are mobile genetic elements that 19 are closely related to retroviruses. Desilenced endogenous retroviruses are associated 20 with human autoimmune disorders and neurodegenerative diseases. C. elegans and 21 related Caenorhabdites contain LTR retrotransposons and, as described here, 22 numerous integrated viral genes including viral envelope genes that are part of LTR 23 retrotransposons. We found that both LTR retrotransposons and endogenous viral 24 elements are silenced by ADARs (adenosine deaminases acting on double-stranded 25 RNA (dsRNA)) together with the endogenous RNAi factor ERI-6/7, a homolog of Mov10 26 helicase, a retrotransposon and retrovirus restriction factor in human. siRNAs 27 Transposons can have profound effects on cellular function such as disruption of gene 53 function by transposon insertion, cell death as a consequence of transposon-induced 54 double stranded breaks, and genomic rearrangements caused by homologous 55 recombination between repeat elements. Retrotransposons and endogenous 56 retroviruses may affect cellular function through overexpression of toxic proteins or the 57 activity of retroviral proteins on endogenous sequences. Palindromic repeat elements 58 such as those formed by adjacent but inverted insertion of vertebrate Alu elements 59 into genes can cause the accumulation of dsRNA. 60 Many RNA viruses replicate via a dsRNA intermediate, which is detected to 61 trigger an interferon-based antiviral response in mammals and an RNA interference 62 response in invertebrates. To avoid an anti-viral response to endogenous palindromic 63 dsRNAs when in fact there is no viral infection, ADARs edit adenosines to inosines in 64 endogenous dsRNA destabilizing the RNA duplex and thus preventing recognition by 65

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MOV10 Provides Antiviral Activity against RNA Viruses by Enhancing RIG-I–MAVS-Independent IFN Induction

Cited by 60 publications

References 43 publications

A direct RNA-protein interaction atlas of the SARS-CoV-2 RNA in infected human cells

A direct RNA-protein interaction atlas of the SARS-CoV-2 RNA in infected human cells

IRF1 Inhibits Antitumor Immunity through the Upregulation of PD-L1 in the Tumor Cell

Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons

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