Nonhuman Transferrin Receptor 1 Is an Efficient Cell Entry Receptor for Ocozocoautla de Espinosa Virus

Caì, Yíngyún; Yú, Shuǐqìng; Mazur, Steven; Liu, Dong; Janosko, Krisztina; Zhāng, Téngfēi; Müller, Marcel A.; Hensley, Lisa E.; Bavari, Sina; Jahrling, Peter B.; Radoshitzky, Sheli R.; Kuhn, Jens H.

doi:10.1128/jvi.02701-13

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…Within clade B, we found that all three compounds retained broad and potent activity against each of the GPs tested, including those from human-pathogenic strains (MACV and GTOV) as well as nonpathogenic members (TCRV and AMAV) (28). Similarly, GPs from clade A/B recombinant viruses, which also use species-specific versions of TfR1 as the primary receptor (29,30,44,(48)(49)(50)(51)(52), were inhibited by all three compounds, although the levels of inhibition were not as severe as those observed for clade B GPs (Fig. 4B).…”

Section: Resultsmentioning

confidence: 94%

“…The OW and NW arenaviruses differ in the entry pathways that they use to enter host cells, recognizing distinct cell surface receptors (29,30,44,(48)(49)(50)(51)(52)(53)(54)(55) and following different intracellular pathways to reach the late endosomes, where virus-cell fusion occurs (reviewed in reference 56). For example, NW clade B viruses use TfR1 as a primary receptor (30,44,48), while both OW and NW clade C viruses use ␣-dystroglycan (␣-DG) (53,55).…”

Section: Resultsmentioning

confidence: 99%

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Novel Arenavirus Entry Inhibitors Discovered by Using a Minigenome Rescue System for High-Throughput Drug Screening

Rathbun

Droniou

Damoiseaux

et al. 2015

J Virol

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Certain members of the Arenaviridae family are category A agents capable of causing severe hemorrhagic fevers in humans. Specific antiviral treatments do not exist, and the only commonly used drug, ribavirin, has limited efficacy and can cause severe side effects. The discovery and development of new antivirals are inhibited by the biohazardous nature of the viruses, making them a relatively poorly understood group of human pathogens. We therefore adapted a reverse-genetics minigenome (MG) rescue system based on Junin virus, the causative agent of Argentine hemorrhagic fever, for high-throughput screening (HTS). The MG rescue system recapitulates all stages of the virus life cycle and enables screening of small-molecule libraries under biosafety containment level 2 (BSL2) conditions. The HTS resulted in the identification of four candidate compounds with potent activity against a broad panel of arenaviruses, three of which were completely novel. The target for all 4 compounds was the stage of viral entry, which positions the compounds as potentially important leads for future development. IMPORTANCEThe arenavirus family includes several members that are highly pathogenic, causing acute viral hemorrhagic fevers with high mortality rates. No specific effective treatments exist, and although a vaccine is available for Junin virus, the causative agent of Argentine hemorrhagic fever, it is licensed for use only in areas where Argentine hemorrhagic fever is endemic. For these reasons, it is important to identify specific compounds that could be developed as antivirals against these deadly viruses.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Novel Arenavirus Entry Inhibitors Discovered by Using a Minigenome Rescue System for High-Throughput Drug Screening

Rathbun

Droniou

Damoiseaux

et al. 2015

J Virol

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“…features of genome expression, genome replication strategy, the presence or absence of various distinctive motifs (for example, polyprotein cleavage sites, internal ribosome entry sites, terminal sequences, structural folds and host range determinants 50 ), and features of global and local genome composition (for example, GC content, dinucleotide frequencies 51 and codon usage). Sequence analyses could thus provide the 'multiple criteria' that are required for classification into species.…”

Section: Virus Taxonomy In the Age Of Metagenomicsmentioning

confidence: 99%

Virus taxonomy in the age of metagenomics

et al. 2017

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| The number and diversity of viral sequences that are identified in metagenomic data far exceeds that of experimentally characterized virus isolates. In a recent workshop, a panel of experts discussed the proposal that, with appropriate quality control, viruses that are known only from metagenomic data can, and should be, incorporated into the official classification scheme of the International Committee on Taxonomy of Viruses (ICTV). Although a taxonomy that is based on metagenomic sequence data alone represents a substantial departure from the traditional reliance on phenotypic properties, the development of a robust framework for sequence-based virus taxonomy is indispensable for the comprehensive characterization of the global virome. In this Consensus Statement article, we consider the rationale for why metagenomic sequence data should, and how it can, be incorporated into the ICTV taxonomy, and present proposals that have been endorsed by the Executive Committee of the ICTV. NATURE REVIEWS | MICROBIOLOGY VOLUME 15 | MARCH 2017 | 161 CONSENSUS STATEMENT © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

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“…In contrast, TRIM2 knockdown increased and overexpression decreased infection by Tacaribe virus (Fig 1C). Knockdown of the calcium channel α2δ2 (CACNA2D2) subunit of the VGCC, which we previously showed was needed for infection by NWAs but not OWAs, reduced infection by Tacaribe virus, whereas TfR1 knockdown had no effect on Tacaribe infection, as this virus does not use this receptor on human cells (Fig 1C) [33, 34]. Thus, TRIM2 preferentially restricts infection by NWAs.…”

Section: Resultsmentioning

confidence: 86%

TRIM2, a novel member of the antiviral family, limits New World arenavirus entry

Sarute

Ibrahim

Fagla³

et al. 2019

PLoS Biol

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Tripartite motif (TRIM) proteins belong to a large family with many roles in host biology, including restricting virus infection. Here, we found that TRIM2, which has been implicated in cases of Charcot–Marie–Tooth disease (CMTD) in humans, acts by blocking hemorrhagic fever New World arenavirus (NWA) entry into cells. We show that Trim2 -knockout mice, as well as primary fibroblasts from a CMTD patient with mutations in TRIM2 , are more highly infected by the NWAs Junín and Tacaribe virus than wild-type mice or cells are. Using mice with different Trim2 gene deletions and TRIM2 mutant constructs, we demonstrate that its antiviral activity is uniquely independent of the RING domain encoding ubiquitin ligase activity. Finally, we show that one member of the TRIM2 interactome, signal regulatory protein α (SIRPA), a known inhibitor of phagocytosis, also restricts NWA infection and conversely that TRIM2 limits phagocytosis of apoptotic cells. In addition to demonstrating a novel antiviral mechanism for TRIM proteins, these studies suggest that the NWA entry and phagocytosis pathways overlap.

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Nonhuman Transferrin Receptor 1 Is an Efficient Cell Entry Receptor for Ocozocoautla de Espinosa Virus

Cited by 5 publications

References 27 publications

Novel Arenavirus Entry Inhibitors Discovered by Using a Minigenome Rescue System for High-Throughput Drug Screening

Novel Arenavirus Entry Inhibitors Discovered by Using a Minigenome Rescue System for High-Throughput Drug Screening

Virus taxonomy in the age of metagenomics

TRIM2, a novel member of the antiviral family, limits New World arenavirus entry

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