更新于：2024-11-01

TCRV glycoprotein

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 TCRV glycoprotein 相关的药物

ST-294

靶点

TCRV glycoprotein

作用机制

TCRV glycoprotein 抑制剂

在研机构

SIGA Technologies, Inc.

原研机构

SIGA Technologies, Inc.

在研适应症

病毒感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TCRV glycoprotein 相关的临床结果

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100 项与 TCRV glycoprotein 相关的转化医学

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0 项与 TCRV glycoprotein 相关的专利（医药）

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项与 TCRV glycoprotein 相关的文献（医药）

2024-10-29·mSphere

Discovery and biological confirmation of a highly divergent Tacaribe virus in metatranscriptomic data from neotropical bats

Article

作者: Moreira-Soto, Andres ; Drexler, Jan Felix ; Rossiter, Stephen J. ; Anzolini Cassiano, Murilo Henrique ; Salazar, Jackeline ; Thomas, William R. ; Fischer, Carlo ; Leon, Yolanda ; Dávalos, Liliana M.

ABSTRACT First isolated from neotropical fruit bats in Trinidad in 1956, Tacaribe virus (TCRV) has rarely been detected since. We searched for New World arenavirus reads in roughly 5.7 million sequencing runs available on public databases using Serratus. We recovered a complete genome of a divergent TCRV in metatranscriptomic data derived from heart and eye tissue of an adult male Jamaican fruit-eating bat sampled in the Dominican Republic, 2014. In total, 2,733 reads were mapped resulting in mean coverages of 7.4-fold for the L and 10.2-fold for the S segment. Re-testing original bat specimens showed the highest viral loads in liver tissue (245 copies/mg). Sanger sequencing of PCR amplicons from liver confirmed correctness of and completed the genome recovered from metatranscriptomic data, revealing conserved arenavirus genomic organization, length, intergenic regions, and genome termini. The newly found TCRV strain tentatively named DOM2014 clustered in a basal sister relationship to all other known TCRV strains with which it shared between 83.3%–86.0% genomic and 91.8%–93.7% translated amino acid sequence identity across protein-coding regions. DOM2014 showed a conserved glycine, proline, proline, threonine (GPPT) nucleoprotein motif, which is essential for TCRV interferon β antagonism. Our data confirm the association of TCRV with the bat genus Artibeus put into question by lethal experimental infections and scarce bat-derived TCRV genomic data. Broad genetic diversity and geographic spread require assessments of TCRV strain-associated pathogenicity, particularly for DOM2014 as a highly divergent TCRV strain. Confirmation of genomic database findings by testing original specimens provides robustness to our findings and supports the usefulness of metatranscriptomic studies. IMPORTANCEClade B New World arenaviruses (NWA) include rodent-borne lethal hemorrhagic fever viruses, whereas Tacaribe virus (TCRV) stands out because of its detection in bats and its presumably low zoonotic potential. However, the bat association of TCRV was put into question by lethal experimental neotropical fruit bat infections and rare TCRV detection in bats. Scarce genomic data include near-identical viruses from Caribbean bats and ticks from the US sampled 50 years later. The prototype TCRV isolate used for experimental risk assessments has an extensive passage history in suckling mouse brains. Exploring the true genetic diversity, geographic distribution, and host range of bat-borne NWA is pivotal to assess their zoonotic potential and transmission cycles. We analyzed metatranscriptomic data for evidence of NWA identifying a highly divergent TCRV in bats and confirmed virus detection in original biological materials, supporting the association of TCRV with neotropical bats and warranting investigation of strain-associated TCRV pathogenicity.

2011-03-01·Journal of Virology2区 · 医学

Identification of Two Functional Domains within the Arenavirus Nucleoprotein

2区 · 医学

Article

作者: Gomez, Guillermo A. ; Casabona, Juan Cruz ; D'Antuono, Alejandra ; Lopez, Nora ; Levingston Macleod, Jesica M. ; Loureiro, Maria Eugenia

ABSTRACT Tacaribe virus (TCRV) belongs to the Arenaviridae family. Its bisegmented negative-stranded RNA genome encodes the nucleoprotein (N), the precursor of the envelope glycoproteins, the polymerase (L), and a RING finger matrix (Z) protein. The 570-amino-acid N protein binds to viral RNA, forming nucleocapsids, which are the template for transcription and replication by the viral polymerase. We have previously shown that the interaction between N and Z is required for assembly of infectious virus-like particles (VLPs) (J. C. Casabona et al., J. Virol. 83:7029-7039, 2009). Here, we examine the functional organization of TCRV N protein. A series of deletions and point mutations were introduced into the N-coding sequence, and the ability of the mutants to sustain heterotypic (N-Z) or homotypic (N-N) interactions was analyzed. We found that N protein displays two functional domains. By using coimmunoprecipitation studies, VLP incorporation assays, and double immunofluorescence staining, the carboxy-terminal region of N was found to be required for N-Z interaction and also necessary for incorporation of N protein into VLPs. Moreover, further analysis of this region showed that the integrity of a putative zinc-finger motif, as well as its amino-flanking sequence (residues 461 to 489), are critical for Z binding and N incorporation into VLPs. In addition, we provide evidence of an essential role of the amino-terminal region of N protein for N-N interaction. In this regard, using reciprocal coimmunoprecipitation analysis, we identified a 28-residue region predicted to form a coiled-coil domain (residues 92 to 119) as a newly recognized molecular determinant of N homotypic interactions.

2006-11-15·International Journal of Cancer1区 · 医学

Identification of HLA class I dependent immunogenic peptides from clonotypic TCRβ expressed in cutaneous T‐cell lymphoma

1区 · 医学

Article

作者: Xuan Duc Nguyen ; Edgar Dippel ; Dirk Schadendorf ; Sergij Goerdt ; Jan Müller-Berghaus ; Hiltrud Schönhaber ; Nicole Schwinn ; Mingxia Song ; Harald Klüter ; Jinyang Zeng ; Stefan B. Eichmüller

AbstractThe clonotypic T‐cell receptor (TCR) is a potential target antigen for specific immunotherapy of cutaneous T‐cell lymphoma (CTCL). We identified T‐cell epitopes from the rearranged TCR β chain of the malignant T‐cell population by the “reverse immunology” approach. Peptide‐specific T‐cell lines were generated against predicted epitopes and tested for the recognition of tumor cells and cells transfected with the full‐length DNA coding for TCRV β chain. Two peptides derived from the clonotypic TCRVβ of a HLA‐A2 positive patient could induce peptide‐specific T cells from peripheral blood mononuclear cells of healthy donors and the patient as assessed by IFN‐γ ELISpot assay. Furthermore, the reactive CTLs efficiently recognized autologous Sézary tumor cells, as well as HLA‐A2 positive 293 cells transfected with recombinant plasmid expressing the corresponding TCRVβ29 protein. Similar results were obtained in a HLA‐A3+ patient for TCRVβ7‐Jβ2.7. In conclusion, our experiments show that the TCR β chain harbors epitopes suitable as targets for specific vaccination which might be a promising approach for the specific immunotherapy of cutaneous T‐cell lymphoma patients. © 2006 Wiley‐Liss, Inc.