The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index; 3 of the 6 sources its claims cite were checked for support.
LDLRAD3 is a receptor for Venezuelan equine encephalitis virus
Open accessAbstract
Venezuelan equine encephalitis virus (VEEV) is a neurotropic alphavirus transmitted by mosquitoes that causes encephalitis and death in humans1. VEEV is a biodefence concern because of its potential for aerosol spread and the current lack of sufficient countermeasures. The host factors that are required for VEEV entry and infection remain poorly characterized. Here, using a genome-wide CRISPR–Cas9-based screen, we identify low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3)—a highly conserved yet poorly characterized member of the scavenger receptor superfamily—as a receptor for VEEV. Gene editing of mouse Ldlrad3 or human LDLRAD3 results in markedly reduced viral infection of neuronal cells, which is restored upon complementation with LDLRAD3. LDLRAD3 binds directly to VEEV particles and enhances virus attachment and internalization into host cells. Genetic studies indicate that domain 1 of LDLRAD3 (LDLRAD3(D1)) is necessary and sufficient to support infection by VEEV, and both anti-LDLRAD3 antibodies and an LDLRAD3(D1)–Fc fusion protein block VEEV infection in cell culture. The pathogenesis of VEEV infection is abrogated in mice with deletions in Ldlrad3, and administration of LDLRAD3(D1)–Fc abolishes disease caused by several subtypes of VEEV, including highly virulent strains. The development of a decoy-receptor fusion protein suggests a strategy for the prevention of severe VEEV infection and associated disease in humans. LDLRAD3 is a receptor for infection with Venezuelan equine encephalitis virus, and in mouse models deletion of Ldlrad3 or treatment with a soluble LDLRAD3 decoy molecule abrogates infection and disease caused by this virus.
Overview
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Written from the paper’s full text.
TL;DR
Using a genome-wide CRISPR/Cas9 screen, the authors identify LDLRAD3/Ldlrad3 as a receptor for Venezuelan equine encephalitis virus (VEEV). Ldlrad3 domain 1 mediates VEEV binding and infection, and a Ldlrad3-D1-Fc decoy protein or Ldlrad3 deletion protects mice against pathogenic VEEV strains.
Key findings
- A genome-wide CRISPR/Cas9 screen in ΔB4galt7 Neuro2a cells, using a mouse GeCKO v2 library of 130,209 sgRNAs targeting 20,611 genes and SINV-VEEV-GFP, identified Ldlrad3 as the top candidate required for VEEV infection.
- Editing Ldlrad3 or human LDLRAD3 markedly reduced VEEV infection in neuronal and other cells, and complementation restored infection; Ldlrad3 bound VEEV particles and enhanced attachment/internalization, with monovalent Ldlrad3-D1 binding VEEV p62-E1 at an affinity of 209 nM.
- Ldlrad3 domain 1 (D1) was necessary and sufficient to support VEEV infection; Ldlrad3-D1-Fc and anti-Ldlrad3 antibodies blocked VEEV infection in cell culture, while Ldlrad3-D1-Fc did not inhibit SINV-EEEV.
- In mice, Ldlrad3 deletions abrogated VEEV pathogenesis, and Ldlrad3-D1-Fc prophylaxis or therapy protected against SINV-VEEV TrD, VEEV TrD, and VEEV ZPC738, including after intracranial VEEV TrD challenge.
Methods
- Genome-wide CRISPR/Cas9 knockout screen in HS-deficient ΔB4galt7 N2a cells with SINV-VEEV-GFP (VEEV IAB strain TrD structural proteins), followed by sorting GFP-negative cells, expansion with anti-VEEV mAbs, repeated infection/sorting, sgRNA sequencing, and MAGeCK analysis.
- Validation used CRISPR/Cas9 editing of mouse Ldlrad3 and human LDLRAD3, lentiviral complementation with full-length, truncated, GPI-anchored, or domain-deleted constructs, infectivity assays, binding/internalization assays, PI-PLC treatment, ELISA, and surface plasmon resonance.
- In vivo studies used C57BL/6J, CD-1, and Ldlrad3 gene-edited mice; Ldlrad3-D1-Fc or isotype control was administered before or after infection with SINV-VEEV TrD, VEEV TrD, or VEEV ZPC738, with survival, weight, clinical disease, viral RNA burden, histology, and in situ hybridization assessed.
Limitations
- The paper states that low levels of residual VEEV infection in Ldlrad3-deficient N2a or SH-SY5Y cells suggest additional factors may contribute to entry; whether laminin-binding proteins or other host factors are involved is undetermined.
- The paper states that mosquitoes lack an apparent Ldlrad3 ortholog and must have separate entry receptors, and that EEEV and WEEV do not require Ldlrad3, so additional receptors for this virus family likely exist.
- The text makes evident that in vivo studies were not blinded, mice were randomly assigned to treatment groups, and no sample-size calculations were performed; sample sizes were based on previous in vivo virus challenge experiments.
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Claims the paper makes
42 Own result · 10 Own method · 5 Own interpretation · 1 Supported so far · 1 Partly supported · 1 Couldn’t confirm · accuracy not yet measured
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ldlrad3 binds directly to VEEV particles and enhances virus attachment and internalization into cells.”
- Also stated in: § Abstract · plain
“The Ldlrad3-D1-Fc variants and Ldlrad3-D1+D2-Fc fusion protein bound to VEEV but not to CHIKV virus-like particles (VLPs); however, Ldlrad3-D2-Fc did not bind to VEEV VLPs (Fig 3b).”
- Also stated in: § Abstract · plain
“We found a slow association rate, a long half-life, and an affinity of 209 nM (Fig 3d).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using a genome-wide CRISPR/Cas9-based screen, we identify Ldlrad3, a highly conserved member of the scavenger receptor superfamily, as a receptor for VEEV.”
- Also stated in: § Abstract · plain
“The top candidate was low-density lipoprotein (LDL) receptor class A domain containing 3 (Ldlrad3) (Fig 1a), a conserved plasma membrane protein of the LDL scavenger receptor family found in mammals, birds, reptiles, amphibians, and fish (Extended Data Fig 1d).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“both anti-Ldlrad3 antibodies and a Ldlrad3-D1-Fc fusion protein block VEEV infection in cell culture.”
- Also stated in: § Abstract · plain
“pre-treatment of ΔB4galt7 N2a cells with anti-Ldlrad3 immune but not naïve serum blocked infection of SINV-VEEV-GFP but not SINV-EEEV-GFP (Fig 2e).”
- Also stated in: § Abstract · plain
“pre-treatment of primary cells with anti-Ldlrad3 immune serum reduced SINV-VEEV-GFP TrD infection (Fig 2f).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“however, Ldlrad3-D2-Fc did not bind to VEEV VLPs (Fig 3b).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ectopic expression of LDLRAD3 in ΔLdlrad3 ΔB4galt7 N2a cells also increased SINV-VEEV-GFP TrD infection (Fig 1l and Extended Data Fig 2i).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“VEEV ZPC738 viral RNA levels were abrogated in mice treated with Ldlrad3-D1-Fc (Fig 4f–g and Extended Data Fig 8a and c).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“treatment with Ldlrad3-D1-Fc via intraperitoneal injection protected mice against intracranial challenge with VEEV TrD (Fig 4h and Extended Data Fig 7e–f).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Administration of Ldlrad3-D1-Fc at 24 h post-infection also protected mice against weight loss and lethality (Fig 4c and Extended Data Fig 7b).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In situ hybridization (brown) of Ldlrad3 (olfactory bulb, cortex, thalamus, and hippocampus) from WT mice (left panels).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Extended Data
plainn = 5- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ldlrad3-D1 does not bind appreciably to CHIKV p62-E1.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Extended Data
plain- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 16
- It may state two separate claims as one. 18
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Because some alphaviruses can attach to cells via engagement of HS11–13, we performed the screen using mouse Neuro2a (termed N2a hereafter) cells that were edited to lack expression of B4galt7 (Extended Data Fig 1b), an enzyme required for glycosaminoglycan (GAG) and HS biosynthesis.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
What the sources say
- Supportedcites [11] Ryman, K. D. et al. Heparan sulfate binding can contribute to the neurovirulence of neuroadapted and nonneuroadapted Sindbis viruses. J. Virol. 81, 3563–3573 (2007). source
The citation supports the sentence’s background premise that some alphaviruses attach to cells through heparan sulfate, not the citing authors’ choice of CRISPR-screen cells. In “Dependence of binding/infectivity on HS-mediated attachment” (page not provided), the paper reports HS-dependent attachment and infection by Sindbis virus variants. It does not need to document the citing authors’ B4galt7 editing to support the cited premise. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [12] Gardner, C. L., Ebel, G. D., Ryman, K. D. & Klimstra, W. B. Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence. Proc. Natl Acad. Sci. USA 108, 16026–16031 (2011). source
- Not checked — no full text of the sourcecites [13] Tanaka, A. et al. Genome-wide screening uncovers the significance of N-sulfation of heparan sulfate as a host cell factor for Chikungunya virus infection. J. Virol. 91, e00432-17 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“sample sizes were determined based on previous in vivo virus challenge experiments4.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Mouse experiments.
What the sources say
- Partly supportedcites [4] Zhang, R. et al. Mxra8 is a receptor for multiple arthritogenic alphaviruses. Nature 557, 570–574 (2018). sourceExperimental — accuracy not yet measured
The Methods section (“Mouse experiments”; page not provided) says sample sizes were estimated to detect a 3- to 5-fold difference in the in vivo experiments. It does not say those estimates were based on previous in vivo virus challenge experiments. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The insertion of GFP has minimal effects on virus infection and replication20,24.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Extended Data
What the sources say
- Not checked — no full text of the sourcecites [20] Sun, C., Gardner, C. L., Watson, A. M., Ryman, K. D. & Klimstra, W. B. Stable, high-level expression of reporter proteins from improved alphavirus expression vectors to track replication and dissemination during encephalitic and arthritogenic disease. J. Virol. 88, 2035–2046 (2014). source
- Could not verifycites [24] Kim, A. S. et al. Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein. Nat. Microbiol. 4, 187–197 (2019). sourceExperimental — accuracy not yet measured
The Results section (‘Generation of anti-EEEV mAbs’; page unavailable) says that a SINV-EEEV chimera replicated efficiently in cell culture. The Methods section (‘Cell lines and plasmids’; page unavailable) describes that chimera, but neither passage addresses GFP insertion into SINV-VEEV or its effects on infection and replication. Searches for GFP insertion and a fluorescent reporter found no passage that settles the claim. (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gene editing of mouse Ldlrad3 or human LDLRAD3 results in markedly reduced viral infection of neuronal cells, which is restored upon complementation.”
- Also stated in: § Abstract · plain
“Markedly reduced infection of SINV-VEEV-GFP TrD was detected in ΔB4galt7 ΔLdlrad3 cells under single- or multi-step growth conditions (Fig 1b–d). Complementation with a full-length, seed-sequence Ldlrad3 variant restored expression and infectivity (Fig 1b–d and Extended Data Fig 2c and i).”
- Also stated in: § Abstract · plain
“A loss of LDLRAD3 expression in SH-SY5Y cells resulted in decreased SINV-VEEV TrD infection, which was restored by expression of the full-length but not truncated isoform of Ldlrad3 (Fig 1m–n and Extended Data Fig 2h).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ldlrad3 binds directly to VEEV particles and enhances virus attachment and internalization into cells.”
- Also stated in: § Abstract · plain
“SINV-VEEV TrD showed reduced binding at 4°C to ΔLdlrad3 ΔB4galt7 cells compared to control ΔB4galt7 N2a cells and increased binding to cells expressing Ldlrad3 (Fig 2a).”
- Also stated in: § Abstract · plain
“When virus internalization assays were performed at 37°C, less SINV-VEEV TrD RNA was measured in ΔLdlrad3 ΔB4galt7 cells, and increased levels were detected in cells expressing Ldlrad3 (Fig 2b).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Genetic studies indicate that domain 1 (D1) of Ldlrad3 is necessary and sufficient to support VEEV infection, and both anti-Ldlrad3 antibodies and a Ldlrad3-D1-Fc fusion protein block VEEV infection in cell culture.”
- Also stated in: § Abstract · hedged
“Whereas D1+D2 supported SINV-VEEV-GFP TrD infection, D2+D3 did not, consistent with a role for D1 in binding VEEV (Fig 3e and Extended Data Fig 6h).”
- Also stated in: § Abstract · plain
“Despite being expressed at lower levels, D1 alone still promoted SINV-VEEV-GFP TrD infection (Extended Data Fig 6i).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Abstract · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whereas expression of full-length Ldlrad3 restored infection in ΔLdlrad3 ΔB4galt7 N2a cells, Δ32 Ldlrad3 did not (Fig 3f).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found a slow association rate, a long half-life, and an affinity of 209 nM (Fig 3d).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed that human dermal microvascular endothelial cells and dermal fibroblasts, but not peripheral blood monocytes and peripheral blood T cells, express LDLRAD3 and were permissive for SINV-VEEV-GFP TrD infection (Extended Data Fig 5b).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Founder lines (Δ11 and Δ14 nucleotides) were confirmed and genotyped by next-generation sequencing.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Generation of mice with deletions in Ldlrad3.
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Histological evaluation of VEEV ZPC738-infected brains showed neuronal injury and hemorrhage, which was absent in mice treated with Ldlrad3-D1-Fc (Extended Data Fig 8b and d).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Ldlrad3 mRNA was detected in many tissues in wild-type mice, whereas no signal was detected in ΔLdlrad3 mice by qRT-PCR (Extended Data Fig 10b–c).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The Ldlrad3-D1-Fc variants and Ldlrad3-D1+D2-Fc fusion protein bound to VEEV but not to CHIKV virus-like particles (VLPs); however, Ldlrad3-D2-Fc did not bind to VEEV VLPs (Fig 3b).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whereas D1+D2 supported SINV-VEEV-GFP TrD infection, D2+D3 did not, consistent with a role for D1 in binding VEEV (Fig 3e and Extended Data Fig 6h).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Two human tumor cell lines (Jurkat and Raji cells) lack surface expression of LDLRAD3 and were resistant to SINV-VEEV-GFP TrD infection (Extended Data Fig 3a and c).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plainn = 2- Asserted: passes — The authors put it forward as true.
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In the paper
“A similar LDLRAD3-D1 fusion protein with human IgG1 Fc domain also bound to VEEV but not to CHIKV VLPs (Fig 3c and Extended Data Fig 6b–c).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“at 4 days post-infection (dpi), SINV-VEEV TrD viral RNA was largely absent from sites normally targeted by VEEV including the brain of mice administered Ldlrad3-D1-Fc, whereas high levels were present in the control mAb-treated animals (Fig 4b).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ldlrad3-D1+D2-Fc, but not Ldlrad3-D2-Fc, inhibited SINV-VEEV-GFP TrD infection comparably to Ldlrad3-D1-Fc (Fig 3i).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The full-length human isoform of LDLRAD3 is 96% identical to mouse Ldlrad3 and differs by only three amino acids in the ectodomain (Extended Data Fig 1d).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One sgRNA gave rise to two out-of-frame deletion variants (Δ11 and Δ14 nucleotides) (Extended Data Fig 9b).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While substantially reduced infection was observed with VEEV TrD, no difference was observed with EEEV (Fig 1f). This phenotype was confirmed with SINV-EEEV and extended to SINV-WEEV (MacMillan) (Fig 1g).”
- Also stated in: § Abstract · plain
“Similarly, we observed no loss of infection by arthritogenic alphaviruses (SINV and MAYV), an unrelated rhabdovirus (Vesicular stomatitis virus), or an unrelated flavivirus (West Nile virus) when Ldlrad3 was edited (Fig 1h–k).”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Abstract · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The Ldlrad3 sgRNA target sequence was mutated synonymously (sgRNA-1: ACCAACGAGTGCAACATCCC to ACAAATGAATGTAATATTCC; sgRNA-2: AGCATCACGTACGCCATCAT to TCTATTACTTATGCTATTAT) to prevent editing of the re-introduced gene.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Complementation experiments.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Ldlrad3 gene-editing was validated by next generation sequencing on an Illumina HiSeq 2500 platform (Genome Technology Access Center, Washington University) with 300 base pair paired-end sequencing.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Gene validation.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“mice were randomly assigned to treatment groups”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Mouse experiments.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In vivo studies were not blinded”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Mouse experiments.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Anti-HCV mAb H77.39 was included as a negative isotype control.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Ldlrad3-Fc inhibition assays.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Immobilized CHIKV p62-E1 served as a reference surface to correct for bulk refractive index changes.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Surface plasmon resonance.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All experiments were conducted with approval of the Institutional Animal Care and Use Committee at Washington University School of Medicine (Assurance number A3381-01) or University of Pittsburgh.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Mouse experiments.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mosquitoes, a natural host for VEEV, lack an apparent Ldlrad3 ortholog and thus must have separate entry receptors.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
- Rests on an assumption: Mosquitoes lack an apparent Ldlrad3 ortholog.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, since EEEV and WEEV do not require Ldlrad3 for infection, additional receptors for this virus family likely exist.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No sample-size calculations were performed to power each study.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Mouse experiments.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A ZIKV RNA probe (Advanced Cell Diagnostics #467771) was used as a negative control.”
§ LDLRAD3 is a receptor for Venezuelan equine encephalitis virus > METHODS > Histology and in situ viral RNA hybridization.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Host factors required for VEEV entry and infection remain poorly characterized.
“The host factors required for VEEV entry and infection remain poorly characterized.”
The paper relies on this without support.
No physiologically relevant entry receptor for VEEV has been established.
“For VEEV, no physiologically relevant entry receptor has been established, although a laminin-binding protein reportedly enhances infection of mosquito and human cells6,7.”
The paper relies on this without support.
Mosquitoes lack an apparent Ldlrad3 ortholog.
“Mosquitoes, a natural host for VEEV, lack an apparent Ldlrad3 ortholog and thus must have separate entry receptors.”
The paper relies on this without support.
Ldlrad3-D1-Fc and Ldlrad3-D1-HRV-Fc have equivalent VEEV binding and neutralizing activity.
“which have equivalent VEEV binding and neutralizing activity”
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BackgroundA molecular understanding of alphavirus entry and antibody protection
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MFSD6 is an entry receptor for enterovirus D68
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Self-citationMFSD6 is an entry receptor for respiratory enterovirus D68
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BackgroundAsialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes
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Orchestration of antiviral responses within the infected central nervous system
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“Correspondingly, immature OSNs are more prone to VEEV infection than mature OSNs [18, 19].”
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“Rubella virus Myelin oligodendrocyte glycoprotein (MOG) Oligodendrocyte [133] Glioma [134] Multiple sclerosis [135] Venezuelan Equine encephalitis virus Low-density lipoprotein receptor class A domaincontaining 3 (LDLRAD3) Neuronal cells [136] Breast Cancer [137]”
BackgroundMultiple LDLR family members act as entry receptors for yellow fever virus
Chong, Z., Hui, S., Qiu, X., Palakurty, S., Sariol, A., Kaszuba, T., Nguyen, M. N., Li, P., Raju, S., Hall, P. D., et al. (2025) · Nature · doi:10.1038/s41586-025-09689-2 · Cited by 26
“In comparison to the LDLRA3-LA1–Fc decoy molecule, which inhibits VEEV infection in mice 39,40 , the levels of LRP4-LBD–Fc and LRP4-LA(6–8)–Fc in the serum were lower (Extended Data Fig.”
Self-citationThe VLDLR entry receptor is required for the pathogenesis of multiple encephalitic alphaviruses
Palakurty, S., Raju, S., Sariol, A., Chong, Z., Wagoner, N., Ma, H., Zimmerman, O., Adams, L. J., Carmona, C., Liu, Z., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114809 · Cited by 22
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The receptor VLDLR binds Eastern Equine Encephalitis virus through multiple distinct modes
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“5c Western blot: it is better to show the whole blot rather than the singled-out bands.”
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“LDLRAD3, a recently identified receptor of VEEV [16] (Table 5), is present in olfactory neurons [94], specifically in high levels within olfactory sensory neurons [83], suggesting that LDLRAD3 contributes to enhanced tropism of the olfactory sensory neurons.”
Tang, N., Zhang, Y., Shen, Z., Yao, Y., & Nair, V. (2021) · The CRISPR Journal · doi:10.1089/crispr.2021.0017 · Cited by 22
The application of CRISPR/Cas9–based genome-wide screening to disease research
Chen, X., Zheng, M., Lin, S., Huang, M., Chen, S., & Chen, S. (2024) · Molecular and Cellular Probes · doi:10.1016/j.mcp.2024.102004 · Cited by 21
Kafai, N. M., Jáňová, H., Cain, M. D., Alippe, Y., Muraro, S. P., Sariol, A., Elam-Noll, M., Klein, R. S., & Diamond, M. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112946 · Cited by 18
“Primer and probe sequences used to determine RNA levels are published 42 and as follows: VEEV ZPC738 nsP3 forward: 5 ′ -CAAGTCGAGGCAGACATTCA-3 ′ ; VEEV ZPC738 nsP3 reverse: 5 ′ -CAGGGTGTCAAGGATGGATAAA-3 ′ ; VEEV ZPC738 nsP3 probe: 5 ′ -/56-FAM/TGGTCCATT/ZEN/CCTCATGCATCCGAC/3IABkFQ/−3 ′ (Integrated…”
InfluentialSelf-citationOechslin, N., Silva, N. D., Ankavay, M., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2307423120 · Cited by 18
“Genome - wide CRISPR/Cas9 screens have been mainly used to study cytolytic viruses, allowing for convenient selection of virus - resistant cells and the identification of host factors required for virus entry, genome translation, replication, or virus - induced cell death (11–14).”
BackgroundStructural Insights into Alphavirus Assembly Revealed by the Cryo-EM Structure of Getah Virus
Wang, M., Sun, Z., Cui, C., et al. (2022) · Viruses · doi:10.3390/v14020327 · Cited by 17
“E2 is one of the major antigens of alphaviruses, and is also responsible for binding host cell receptors [24].”
BackgroundSu, W. C., Hong, T., Feng, B., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1075848 · Cited by 17
“LDLRAD3 encodes Low Density Lipoprotein Receptor Class A Domain Containing 3 and acts upstream of or within receptor-mediated endocytosis and regulation of protein processing (19).”
BackgroundThe neonatal Fc receptor is a cellular receptor for human astrovirus
Ingle, H., Molleston, J. M., Hall, P. D., Bui, D., Wang, L., Bhatt, K. D., Foster, L. R., Antia, A., Ding, S., Lee, S., et al. (2024) · Nature Microbiology · doi:10.1038/s41564-024-01855-y · Cited by 19
“No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications 55,56 .”
Self-citationCryo-EM structures of alphavirus conformational intermediates in low pH–triggered prefusion states
Chen, C.-L., Klose, T., Sun, C., Kim, A. S., Buda, G., Rossmann, M. G., Diamond, M., Klimstra, W. B., & Kuhn, R. J. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2114119119 · Cited by 16
Self-citationCain, M. D., Klein, N. R., Jiang, X., Salimi, H., Wu, Q., Miller, M. J., Klimstra, W. B., & Klein, R. S. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02960-1 · Cited by 16
Self-citationEstablishment of a pig CRISPR/Cas9 knockout library for functional gene screening in pig cells
Yu, C., Zhong, H., Yang, X., et al. (2021) · Biotechnology Journal · doi:10.1002/biot.202100408 · Cited by 16
LRP8 is an entry receptor for tick-borne encephalitis viruses
Li, P., Hui, S., Chong, Z., Escaffre, O., Nguyen, M. N., Muraro, S. P., Jáňová, H., Ma, H., Cao, S., Kaszuba, T., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2525771122 · Cited by 15
“LDLR family members have been identified as candidate entry receptors for several alphaviruses [Venezuelan equine encephalitis virus (VEEV) - LDLRAD3, Western equine encephalitis virus (WEEV) - LDLR or VLDLR, Eastern equine encephalitis virus (EEEV) - VLDLR or LRP8, and Semliki Forest virus (SFV) - VLDLR or LRP8] (12–…”
Self-citationMa, H., Albe, J. R., Gilliland, T. H., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1009946 · Cited by 15
Self-citationSpecies-specific MARCO-alphavirus interactions dictate chikungunya virus viremia
Li, F. S., Carpentier, K. S., Hawman, D. W., Lucas, C. J., Ander, S. E., Feldmann, H., & Morrison, T. E. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112418 · Cited by 15
The immune system of prokaryotes: potential applications and implications for gene editing
Liu, S. M., Liu, H., Wang, X., & Shi, L. (2024) · Biotechnology Journal · doi:10.1002/biot.202300352 · Cited by 16
PCDH10 is a neuronal receptor for western equine encephalitis virus
Yang, Y., Zhao, L., Li, Z., et al. (2024) · Cell Research · doi:10.1038/s41422-024-01031-1 · Cited by 15
The many ways in which alphaviruses bind to cells
Raju, S., Adams, L. J., & Diamond, M. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.11.006 · Cited by 14
Self-citationMYADM binds human parechovirus 1 and is essential for viral entry
Qiao, W., Richards, C. M., Kim, Y., Zengel, J. R., Ding, S., Greenberg, H. B., & Carette, J. E. (2024) · Nature Communications · doi:10.1038/s41467-024-47825-0 · Cited by 14
“The assays were conducted following the methods described previously with slight modi fi cation 39 .”
Insights into mosquito-borne arbovirus receptors
Liu, J., Quan, Y., Tong, H., Zhu, Y., Shi, X., Liu, Y., & Cheng, G. (2024) · Cell Insight · doi:10.1016/j.cellin.2024.100196 · Cited by 14
“Also, The C-terminal of human laminin-binding protein (LBP) binds to the VEEV E2 protein, and related antibodies reduce viral replication (Malygin et al., 2009).”
BackgroundMethod3-Cyanoazolo[5,1-c][1,2,4]triazines: synthesis and antiviral activity
Sapozhnikova, I. M., Ulomsky, E. N., Русинов, В. Л., et al. (2021) · Chemistry of Heterocyclic Compounds · doi:10.1007/s10593-021-02925-3 · Cited by 14
A Structural Perspective on the Alphavirus Life Cycle
Luo, D., Tan, Y. B., Law, M. C. Y., & Jin, J. (2025) · Annual Review of Virology · doi:10.1146/annurev-virology-093022-010359 · Cited by 13
Host entry factors of Rift Valley Fever Virus infection
Ganaie, S. S., Leung, D. W., Hartman, A. L., & Amarasinghe, G. K. (2023) · Advances in virus research · doi:10.1016/bs.aivir.2023.09.001 · Cited by 15
Xie, Y., Cao, J., Gan, S., Xu, L.-D., Zhang, D., Qian, S., Xu, F., Ding, Q., Schoggins, J. W., & Fan, W. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012312 · Cited by 12
Genome-wide CRISPR screens and their applications in infectious disease
Srivastava, K., & Pandit, B. (2023) · Frontiers in Genome Editing · doi:10.3389/fgeed.2023.1243731 · Cited by 12
Tong, S. J. M., Jun, K. T. Y., & Carissimo, G. (2024) · Virulence · doi:10.1080/21505594.2024.2355201 · Cited by 12
Lipoprotein receptors: A little grease for enveloped viruses to open the lock?
Cosset, F., & Denolly, S. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107849 · Cited by 11
LRP6 Is a Functional Receptor for Attenuated Canine Distemper Virus
Gradauskaite, V., Inglebert, M., Doench, J. G., Scherer, M., Dettwiler, M., Wyss, M., Shrestha, N., Rottenberg, S., & Plattet, P. (2023) · mBio · doi:10.1128/mbio.03114-22 · Cited by 11
Yang, J., Liu, T., Chen, Y.-C., et al. (2023) · Clinical Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s428788 · Cited by 11
“50 GWAS data also have indicated an association between LDLRAD3 and the secretion of melatonin.”
Lucas, C. J., Davenport, B., Carpentier, K. S., Tinega, A. N., & Morrison, T. E. (2022) · Journal of Virology · doi:10.1128/jvi.00064-22 · Cited by 10
Virus structures revealed by advanced cryoelectron microscopy methods
Zhu, D., Cao, D., & Zhang, X. (2023) · Structure · doi:10.1016/j.str.2023.09.008 · Cited by 10
LDL receptor in alphavirus entry: structural analysis and implications for antiviral therapy
Wang, N., Merits, A., Veit, M., Lello, L. S., Kong, S., Jiao, H., Chen, J., Wang, Y., Dobrikov, G. M., Rey, F. A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49301-1 · Cited by 11
“2a) 15 .”
BackgroundStructural basis for plasticity in receptor engagement by an encephalitic alphavirus
Raju, S., Palakurty, S., Sariol, A., Wagoner, N., Adams, L. J., Hui, S., Klimstra, W. B., Fremont, D. H., & Diamond, M. (2025) · Cell · doi:10.1016/j.cell.2025.02.036 · Cited by 11
“16,44 In brief, constructs were co-transfected with human LRPAP1 (RAP) chaperone gene (residues 1–353) at a (4:1 ratio) with Expifectamine 293 reagent into Expi293 cells (Thermo Fisher) according to the manufacturer’s instructions.”
Self-citationLRP1 facilitates Jamestown Canyon virus infection of neurons
Frey, Z. D., Price, D. A., Connors, K. A., Rush, R. E., Brown, G. S., Sterling, C. E., Fatma, F., Schwarz, M. M., Ganaie, S. S., Cui, X., et al. (2025) · Journal of Virology · doi:10.1128/jvi.01841-25 · Cited by 13
“LDLRs have been implicated in mediating cellular entry of a variety of arboviruses, including multiple alphaviruses and bunyaviruses (15, 17–22, 38–40, 46).”
Structural basis of Semliki Forest virus entry using the very-low-density lipoprotein receptor
Li, Y., Zhao, Z., Liu, S., Wang, H., Sun, J., Chai, Y., Zhou, J., Wang, Y., Shi, Y., Song, H., et al. (2023) · hLife · doi:10.1016/j.hlife.2023.11.001 · Cited by 10
Glycosaminoglycan binding by arboviruses: a cautionary tale
Alcorn, M. D. H., & Klimstra, W. B. (2022) · Journal of General Virology · doi:10.1099/jgv.0.001726 · Cited by 10
Self-citationAnimal models of alphavirus infection and human disease
Lucas, C. J., & Morrison, T. E. (2022) · Advances in virus research · doi:10.1016/bs.aivir.2022.07.001 · Cited by 9
Zhang, Y., Yu, J., Tan, L., Wang, X., Li, R., & Kim, D. (2021) · The Journal of Microbiology · doi:10.1007/s12275-021-1361-8 · Cited by 9
Broad Host Tropism of Flaviviruses during the Entry Stage
Zhang, Y., Yan, Y., Li, S., Yuan, F., Wen, D., Jia, N., Xiong, T., Zhang, X., & Zheng, A. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.05281-22 · Cited by 8
Han, L., Song, S., Feng, H., Ma, J., Wei, W., & Si, F. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.125514 · Cited by 9
Developing a Prototype Pathogen Plan and Research Priorities for the Alphaviruses
Powers, A. M., Williamson, L. E., Carnahan, R. H., Crowe, J. E., Hyde, J., Jonsson, C. B., Nasar, F., & Weaver, S. C. (2022) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiac326 · Cited by 12
Unraveling the complexities of neurotropic virus infection and immune evasion
Verma, A. K., & Perlman, S. M. (2025) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00185-23 · Cited by 9
Alcorn, M. D. H., Sun, C., Gilliland, T. C., Lukash, T., Crasto, C. M., Raju, S., Diamond, M., Weaver, S. C., & Klimstra, W. B. (2025) · Nature Communications · doi:10.1038/s41467-025-62513-3 · Cited by 8
“All mice treated with the LDLRAD3 LA1-Fc control before infection succumbed to infection (Fig.”
InfluentialSelf-citationCarriquí-Madroñal, B., Sheldon, J., Duven, M., et al. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011759 · Cited by 8
“However, this result should be challenged in other cell types, as VEEV is a neurotropic virus and hCoV-229E infects mainly human airway epithelia [84,85].”
BackgroundYang, D., Wang, N., Du, B., Sun, Z., Wang, S., He, X., Wang, J., Zheng, T., Chen, Y., Wang, J., et al. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012770 · Cited by 7
Ma, B., Cao, Z., Ding, W., Zhang, X., Xiang, Y., & Cao, D. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115724 · Cited by 9
Alvarez, P. A., Tang, A., Winters, D., Kaushal, P., Medina, A., Nieto, M., Kaczor‐Urbanowicz, K. E., Amant, F. S., Reyes, B. R., Kaake, R. M., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116305 · Cited by 7
Mazloum, A., Karagyaur, M. N., Chernyshev, R., van Schalkwyk, A., Ma, J., Fu, Q., & Sprygin, A. V. (2023) · Frontiers in Veterinary Science · doi:10.3389/fvets.2023.1180621 · Cited by 10
“Recently, a genome-wide screen using CRISPR/Cas9 was conducted to identify host factors that may potentially participate in the replication of certain viruses, such as SARS-CoV-2 (90), HIV (91), arthritic alphaviruses (92), Coxsackie virus (93), Venezuelan equine encephalitis virus (VEEV) (94) and influenza virus (95).”
BackgroundInhibitors of the Structural and Nonstructural Proteins of Alphaviruses
Metibemu, D. S., Adeyinka, O. S., Falode, J. A., Crown, O. O., & Ogungbe, I. V. (2024) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.4c00254 · Cited by 7
Neumann, K., Vujinovic, A., Kamara, S., Zwicky, A., Baldauf, S., & Bode, J. W. (2023) · RSC Chemical Biology · doi:10.1039/d2cb00234e · Cited by 7
Expanding the Hepatitis E Virus Toolbox: Selectable Replicons and Recombinant Reporter Genomes
Oechslin, N., Ankavay, M., Moradpour, D., et al. (2023) · Viruses · doi:10.3390/v15040869 · Cited by 7
“This screening approach has proven over the last years to be extremely powerful for virus–host interaction study with numerous articles in the literature (among many others [29,82,83]), however, none concerned HEV.”
BackgroundThe alphavirus determinants of intercellular long extension formation
Martin, C. K., Wan, J. J., Yin, P., Morrison, T. E., Messer, W. B., Rivera‐Amill, V., Lai, J. R., Grau, N., Rey, F. A., Couderc, T., et al. (2024) · mBio · doi:10.1128/mbio.01986-24 · Cited by 6
Pseudorabies virus upregulates low-density lipoprotein receptors to facilitate viral entry
Ma, Y.-X., Chai, Y.-J., Han, Y.-Q., Zhao, S., Yang, G., Wang, J., Ming, S., & Chu, B. (2023) · Journal of Virology · doi:10.1128/jvi.01664-23 · Cited by 6
“Recently, it was discovered that LDLR is also a receptor for the Venezuelan equine encephalitis virus (58) and the Rift Valley fever virus (59).”
BackgroundNawrooz, M. S., Taher, W. M., Alwan, M., Jawad, M. J., Mushtaq, H., & Allela, O. Q. B. (2025) · Archives of Microbiology · doi:10.1007/s00203-025-04632-5 · Cited by 5
“Consequently, therapeutic strategies targeting the LDLR-CCHFV interac-tion—such as sLDLR decoys, blocking antibodies, or small molecules—hold promise for treating CCHFV infection (Xu et al. 2024; Ganaie et al. 2021; Clark et al. 2022; Ma et al. 2020).”
Hidden in Plain Sight: Alphavirus Persistence and Its Potential for Driving Chronic Pathogenesis
Guzman, M. D. M. V., Yao, Z., Li, M. M. H., & Noval, M. G. (2025) · Viruses · doi:10.3390/v18010030 · Cited by 6
Wani, M. M., Cooper, J. M., Migliorini, M. M., & Strickland, D. K. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.110227 · Cited by 5
“Beyond these core family members, there are also some distant members of the family that include: LRP5/6, SORL1, LRP3, LRP12, LRP10 and LDLRAD3, a small receptor that along with the VLDLR mediates cellular entry of the Venezuelan equine encephalitis virus (15, 16).”
A high-throughput screening assay to identify inhibitory antibodies targeting alphavirus release
Ramjag, A. T., Cutrone, S., Lü, K., Crasto, C. M., Jin, J., Bakkour, S., Carrington, C. V. F., & Simmons, G. (2022) · Virology Journal · doi:10.1186/s12985-022-01906-y · Cited by 6
“Several cellular receptors have been identified [21, 22] including a pan-arthritogenic alphaviral receptor Mxra8 [23] for CHIKV, MAYV, Ross River virus, and O’nyong nyong virus.”
BackgroundChen, J., Fang, M., Li, Y., Ding, H., Zhang, X., Jiang, X., Zhang, J., Zhang, C. C., Lu, Z., & Luo, M. (2024) · Life Medicine · doi:10.1093/lifemedi/lnae031 · Cited by 6
“L i f e M e d i c i n e [73, 126–130].”
LDL receptor–mediated endocytosis of Escherichia coli α-hemolysin mediates renal epithelial toxicity
Kuhn, H. W., Smither, M. R., Jin, R. J., Collins, C. A., Ma, H., Sina, J., Gaut, J. P., Diamond, M., & Hunstad, D. A. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2505482122 · Cited by 5
“As noted earlier, LDLR family members are also co - opted for cellular entry by an array of viruses, including encephalitic alphaviruses ( 42 , 43 , 46 , 50 , 60 ), vesicular stomatitis virus ( 44 ), and hepatitis B virus ( 45 ).”
Self-citationLang, S., Lin, X., Wang, S., Sun, W., Yang, Y., Chen, Y., Bao, Z., Feng, W., Wang, Y., & Luo, Y. (2025) · Environment & Health · doi:10.1021/envhealth.5c00072 · Cited by 4
Tetraspanins 10 and 15 support Venezuelan equine encephalitis virus replication in astrocytoma cells
Duven, M., Friedrichs, A., Tomlinson, M. G., et al. (2025) · Molecular Biology of the Cell · doi:10.1091/mbc.e24-12-0574 · Cited by 4
Metadata
- Authors
- Ma, H., Kim, A. S., Kafai, N. M., Earnest, J. T., Shah, A. P., Case, J. B., Basore, K., Gilliland, T. C., Sun, C., Nelson, C. A., Thackray, L. B., Klimstra, W. B., Fremont, D. H., & Diamond, M. S.
- Affiliations
- Washington University in St. Louis (US)
- University of Pittsburgh (US)
- Corresponding author
- Diamond, Michael S.
- ORCID
- Venue
- Nature
- Published
- 2020-11-18
- Volume
- 588
- Issue
- 7837
- Pages
- 308-314
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7769003
- OpenAlex
- W3105847615
- Semantic Scholar
- 9b4dc7dec6bd2485669bd58a0f9c9a413946a3ec
- Cited by
- 161
- References
- 29
- Citations by year
- 2026: 23 · 2025: 38 · 2024: 33 · 2023: 31 · 2022: 19 · 2021: 15 · 2020: 2
- FWCI
- 11.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI153209, U19 AI142790, U19AI142759, HHSN272201700060C, R01AI095436, R01AI143673, T32AI007172)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- Venezuelan equine encephalitis virus, viral receptor, alphavirus, scavenger receptors, viral entry, viral attachment, viral internalization, decoy receptor, neurotropic viruses, encephalitis, CRISPR-Cas9 screen, mouse model
- MeSH terms
- Animals, Cell Line, Encephalitis Virus, Venezuelan Equine, Encephalomyelitis, Venezuelan Equine, Female, Genetic Complementation Test, Humans, Male, Mice, Inbred C57BL, Protein Binding, Receptors, LDL, Receptors, Virus, Mice, Virus Attachment, Virus Internalization, CRISPR-Cas Systems
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