Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus

Miles, Linde A.; Burga, Laura N.; Gardner, Eric E.; Bostina, Mihnea; Poirier, John T.; Rudin, Charles M.

doi:10.1172/jci93472

Cited by 63 publications

(80 citation statements)

References 51 publications

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“…We were consistently unable to detect viral protein in either hWARS-KD or hWARS CRISPR cells after EV-A71 challenge (Figure 1, C and D, and Figure 4D). Recently, CRISPR/Cas9 technology has proven useful in identifying new host cell entry factors or receptors for virus entry, such as the anthrax toxin receptor 1 for the Seneca Valley virus (27). Therefore, CRISPR/Cas9 was also used in this study to confirm the role of hWARS for EV-A71 cell entry.…”

Section: Discussionmentioning

confidence: 99%

Human tryptophanyl-tRNA synthetase is an IFN-γ–inducible entry factor for Enterovirus

Yeung¹,

Jia²,

Yip³

et al. 2018

Journal of Clinical Investigation

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Enterovirus A71 (EV-A71) receptors that have been identified to date cannot fully explain the pathogenesis of EV-A71, which is an important global cause of hand, foot, and mouth disease and life-threatening encephalitis. We identified an IFN-γ-inducible EV-A71 cellular entry factor, human tryptophanyl-tRNA synthetase (hWARS), using genome-wide RNAi library screening. The importance of hWARS in mediating virus entry and infectivity was confirmed by virus attachment, in vitro pulldown, antibody/antigen blocking, and CRISPR/Cas9-mediated deletion. Hyperexpression and plasma membrane translocation of hWARS were observed in IFN-γ-treated semipermissive (human neuronal NT2) and cDNA-transfected nonpermissive (mouse fibroblast L929) cells, resulting in their sensitization to EV-A71 infection. Our hWARS-transduced mouse infection model showed pathological changes similar to those seen in patients with severe EV-A71 infection. Expression of hWARS is also required for productive infection by other human enteroviruses, including the clinically important coxsackievirus A16 (CV-A16) and EV-D68. This is the first report to our knowledge on the discovery of an entry factor, hWARS, that can be induced by IFN-γ for EV-A71 infection. Given that we detected high levels of IFN-γ in patients with severe EV-A71 infection, our findings extend the knowledge of the pathogenicity of EV-A71 in relation to entry factor expression upon IFN-γ stimulation and the therapeutic options for treating severe EV-A71-associated complications.

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Section: Discussionmentioning

confidence: 99%

Human tryptophanyl-tRNA synthetase is an IFN-γ–inducible entry factor for Enterovirus

Yeung¹,

Jia²,

Yip³

et al. 2018

Journal of Clinical Investigation

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“…Structures of mature SVV and the procapsid have been determined previously by crystallography and cryo-EM (19,20), and the binding of ANTXR1 to SVV has been visualized at low resolution (5,19). Structural comparison of the capsids suggests that SVV lies between aphthoviruses and cardioviruses, and is quite distant from enteroviruses (21).…”

Section: Seneca Valley Virus (Svv)mentioning

confidence: 99%

“…SVV selectively infects and lyses neuroendocrine cancer cells, including small-cell lung cancer (SCLC) and pediatric neuroendocrine solid tumors (2)(3)(4). This is stimulating efforts to develop SVV as an oncolytic agent against these tumors, which are a major cause of morbidity and mortality (SCLC alone is responsible for ∼30,000 deaths annually in the United States) (5). Indeed, preclinical and early-phase clinical trials have confirmed the safety and efficacy of SVV as a cancer treatment.…”

Section: Seneca Valley Virus (Svv)mentioning

confidence: 99%

“…Indeed, preclinical and early-phase clinical trials have confirmed the safety and efficacy of SVV as a cancer treatment. Very recently anthrax toxin receptor 1 (ANTXR1) was identified as mediating the initial attachment of SVV to permissive cells and downstream entry events (5).…”

Section: Seneca Valley Virus (Svv)mentioning

confidence: 99%

“…Unlike the wide distribution in adult tissues of another anthrax toxin receptor, ANTXR2 (also known as capillary morphogenesis protein 2, CMG2), ANTXR1 is abundant in tumor cells and the vasculature of developing embryos (7,8). It was reported that among 1,037 cell lines in the Cancer Cell Line Encyclopedia (CCLE), over 63% of cell lines exceed the expression cutoff of ANTXR1 (5). ANTXR1 has an N-terminal extracellular von Willebrand factor type A (vWA) domain containing a metal ion-dependent adhesion site (MIDAS) motif similar to the integrin I domain (6), connected to a C-terminal cytosolic domain by a single transmembrane-spanning domain (6).…”

Section: Seneca Valley Virus (Svv)mentioning

confidence: 99%

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Seneca Valley virus attachment and uncoating mediated by its receptor anthrax toxin receptor 1

Cao

Zhang

Liu

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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wrote the paper.The authors declare no conflict of interest. This article is a PNAS Direct Submission.Published under the PNAS license.Data deposition: The cryo-EM density maps and structures have been deposited in the Protein Data Bank, www.pdb.org, and the Electron Microscopy Data Bank (EMD) [accession nos.: mature particles in pH 8, 6ADT and EMD-9613; mature particles in pH 6, 6ADS and EMD-9612; SVV(full)-ANTXR1 in pH 8, 6ADR and EMD-9611; SVV(full)-ANTXR1 in pH 6, 6ADM and EMD-9608; and SVV(spent)-ANTXR1, 6ADL and EMD-9607].

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Phage‐Derived Oncolytic Viruses with 3C from Seneca Valley Virus for Targeted Therapy of Cervical Cancer

Liu

Zhao

Shi

et al. 2022

Advanced Therapeutics

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Cancer gene therapy based on various gene delivery vectors has some potential but also has obvious disadvantages. In this study, a new M13 phage-based oncolytic virus is constructed that carried the RGD peptides to target tumor cells and the 3C gene of Seneca Valley virus (SVV) preceded by a eukaryotic initial transcriptional region (ITR) to transcribe an oncolytic protein to kill tumor cells. Recombinant virus particles of 1200 nm in length are obtained in large quantities by transfecting the recombinant M13 phage plasmid into the host BL2738 and are investigated in vitro in tumor cells and in vivo in tumor-bearing mice to evaluate their antitumor effect. The experiments using Hela cells confirm that the engineered M13 phage can target and enter Hela cells, and express the SVV 3C protein, resulting in apoptosis of target cells by upregulating the expression of caspase 3. Furthermore, the results of experiments in vivo also show that the recombinant phage significantly inhibits the enhanced tumor volume in nude mice compared to the control groups. The M13 phage may be engineered to fuse with a variety of oncolytic proteins to inhibit the growth of tumor cells in the future, providing a promising phage-based targeted oncolytic reagent.

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Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus

Cited by 63 publications

References 51 publications

Human tryptophanyl-tRNA synthetase is an IFN-γ–inducible entry factor for Enterovirus

Human tryptophanyl-tRNA synthetase is an IFN-γ–inducible entry factor for Enterovirus

Seneca Valley virus attachment and uncoating mediated by its receptor anthrax toxin receptor 1

Phage‐Derived Oncolytic Viruses with 3C from Seneca Valley Virus for Targeted Therapy of Cervical Cancer

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