Endothelial protein C receptor is an entry receptor for Langya virus

Y.-J. Park; J. Song; R. Gen; C. Stewart; S. Lee; D. Veesler

doi:10.64898/2026.11.04.763901

AI summary · DOI: 10.64898/2026.11.04.763901 · bioRxiv: Biochemistry

Endothelial protein C receptor is an entry receptor for Langya virus

Y.-J. Park, J. Song, R. Gen, C. Stewart, S. Lee, D. Veesler

Original paper Published on 06 Nov. 2026 bioRxiv preprint License: CC BY 4.0 Also in: fr

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The essentials

The study identifies EPCR as an entry receptor for Langya virus and characterizes receptor recognition and ortholog use.

Based on the abstract only: check the details in the original paper.

Question

The paper asks which receptor Langya virus uses to enter cells and what determines its recognition of receptor orthologs. It also considers how this receptor use compares with that of related viruses.

Method

The authors investigated binding of the tetrameric Langya virus attachment glycoprotein G to EPCR and examined cell entry using human and shrew EPCR orthologs. They also tested closely related Mojiang pseudoviruses and analyzed the molecular basis of receptor recognition; the abstract does not specify sample sizes or assay details.

Findings

Result The authors identified human EPCR as an entry receptor for Langya virus.
See the passage in the paper
Here, we discovered that human endothelial protein C receptor (EPCR) is an entry receptor for LayV
Result The tetrameric Langya virus attachment glycoprotein G binds EPCR avidly.
See the passage in the paper
the tetrameric LayV attachment glycoprotein (G) binds EPCR avidly.
Result Human and shrew EPCR orthologs promote entry of Langya and closely related Mojiang pseudoviruses.
See the passage in the paper
We found that human and shrew EPCR orthologs promote cell entry of LayV and of the closely related Mojiang pseudoviruses.
Authors’ interpretation The authors argue that EPCR use distinguishes these parahenipaviruses from henipaviruses in their association with reservoir hosts.
See the passage in the paper
These results along with the detection of several Parahenipaviruses in shrews set these pathogens apart from Henipaviruses, which use Pteropid fruit bats as reservoir hosts.

Limitations

The abstract does not report the experimental sample sizes or provide details sufficient to assess the scope of the receptor-entry assays.

Why it matters

The authors argue that the findings can inform surveillance by helping predict EPCR use in newly discovered parahenipaviruses. They also present receptor recognition as a basis for developing and evaluating countermeasures against this emerging group of human pathogens.

Written by AI from the paper. Passages are checked word for word against the text we analysed; the rest may contain errors.

AI-generated keywords: Langya virus; EPCR; viral entry; Parahenipavirus; host range

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Comprehensive Summary
Layman's Summary
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Original abstract

The paper investigates how Langya virus (LayV), an emerging virus associated with febrile illness in humans, enters cells. LayV belongs to the Parahenipavirus group, which is less well understood than the related Henipaviruses. Because receptor use can help explain which species may be susceptible to infection, the authors set out to identify a cellular entry receptor for LayV. The authors report that human endothelial protein C receptor (EPCR) acts as a LayV entry receptor. They also find that the viral attachment glycoprotein G binds strongly to EPCR in a tetrameric form. Their analysis explores the molecular basis of this interaction and features that may affect whether EPCR from different species can support viral entry. The abstract further reports that human and shrew EPCR orthologs promote cell entry by LayV and by pseudoviruses bearing the glycoproteins of the closely related Mojiang virus. These findings may help clarify the ecology of Parahenipaviruses. Several viruses in this group have been detected in shrews, and the ability of shrew EPCR to support entry is consistent with a possible role for shrews as hosts. This contrasts with Henipaviruses, which are associated with Pteropid fruit bats. The authors suggest that their receptor-binding findings could help predict EPCR use by newly discovered Parahenipaviruses, guide surveillance, and inform future countermeasure research. The supplied material includes only the title and abstract, so it does not provide enough information to assess the experimental procedures in detail. For example, it does not describe the specific binding assays, cell systems, structural methods, controls, or methods used to quantify entry. The abstract also reports no numerical measurements, such as binding constants, effect sizes, or sample sizes. The findings should therefore be understood as the authors’ stated conclusions rather than as an independently assessable account of the underlying experiments. The abstract reports receptor use in the tested experimental systems, but it does not establish how commonly EPCR-dependent entry occurs in human tissues, whether EPCR is necessary for infection in living organisms, or how receptor use affects disease severity or transmission. Similarly, pseudovirus results for Mojiang virus do not, by themselves, establish how authentic virus behaves in natural hosts. Overall, the paper identifies EPCR as a LayV entry receptor and reports that human and shrew EPCR orthologs support entry in the tested systems. The findings offer a basis for further research into Parahenipavirus host range, but additional experimental and ecological evidence is needed to clarify their implications for infection in humans and animals.

How Langya Virus May Enter Human Cells

How a virus gets into a cell can offer important clues about which animals it may infect and how it might spread. In “Endothelial protein C receptor is an entry receptor for Langya virus,” Y.-J. Park, J. Song, R. Gen, C. Stewart, S. Lee, and D. Veesler investigate a possible cellular doorway for Langya virus, or LayV. Their central finding is that the human endothelial protein C receptor (EPCR) can act as an entry receptor for the virus in the experimental systems described.

LayV is an emerging virus associated with febrile illness in humans. It belongs to the Parahenipavirus group, which is less well understood than the related Henipaviruses. Identifying the receptors these viruses use can help researchers investigate which species might be susceptible to infection. The paper’s findings offer a starting point for examining LayV’s host range, though they do not settle how infection unfolds in people or animals.

EPCR as a cellular entry point

Viruses often rely on proteins on their surface to attach to molecules on a host cell. In this study, the authors report that LayV uses EPCR as an entry receptor. They also report that LayV’s attachment glycoprotein, G, binds strongly to EPCR when the viral protein is in a tetrameric form. This suggests that the structure of the viral attachment protein may matter to how it engages the receptor.

The authors explore the molecular basis of this interaction and consider features that could influence whether EPCR from different species supports viral entry. Such comparisons are useful because a receptor may vary across animals. Those differences could affect whether a virus can use the receptor in a given species, although receptor compatibility alone does not establish whether that species is infected in nature.

What the species comparison suggests

The abstract reports that both human and shrew EPCR orthologs promote cell entry by LayV in the tested systems. The authors also report entry by pseudoviruses bearing the glycoproteins of Mojiang virus, a closely related virus. These results connect receptor use with questions about the ecology of Parahenipaviruses, several of which have been detected in shrews.

The ability of shrew EPCR to support entry is consistent with a possible role for shrews as hosts of these viruses. It is not, by itself, proof that shrews are natural reservoirs or that they transmit the viruses to people. The authors contrast this possibility with Henipaviruses, which are associated with Pteropid fruit bats. The comparison points to potentially different animal associations among related groups of viruses, while leaving the details of those relationships open for further study.

Why the findings matter—and what remains uncertain

Identifying a receptor can help researchers form testable ideas about host range. The authors suggest that their findings could help predict whether newly discovered Parahenipaviruses may use EPCR, guide surveillance, and inform future countermeasure research. Receptor information may help prioritize which viruses and animal populations warrant closer investigation.

However, the supplied abstract does not describe the experiments in enough detail to evaluate their methods independently. It does not specify the binding assays, cell systems, structural approaches, controls, or methods used to quantify entry. Nor does it provide numerical measurements such as binding constants, effect sizes, or sample sizes. The conclusions should therefore be understood as the authors’ reported findings, rather than as a fully assessable account of the underlying evidence.

The reported results also have important limits. EPCR-dependent entry in tested systems does not establish how often this route is used in human tissues, whether EPCR is necessary for infection in living organisms, or how receptor use affects disease severity or transmission. Likewise, pseudovirus entry involving Mojiang virus glycoproteins does not, on its own, show how authentic Mojiang virus behaves in natural hosts.

A useful lead, not a complete picture

The paper identifies human EPCR as an entry receptor for LayV and reports that human and shrew versions of the receptor support entry in the tested systems. The findings provide a useful basis for investigating Parahenipavirus host range and ecology. Establishing what they mean for infection in people and animals will require additional experimental and ecological evidence, including work that can connect receptor use to infection in living hosts.

Created on 09 Nov. 2026

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Weekly letter Presented in "Biology and medicine this week" of 9 November 2026. Biology and medicine this week: Inherited protection, bacterial clocks and a revised cattle family tree

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Endothelial protein C receptor is an entry receptor for Langya virus

The essentials

Question

Method

Findings

Limitations

Why it matters

Read further

Definitions

How Langya Virus May Enter Human Cells

EPCR as a cellular entry point

What the species comparison suggests

Why the findings matter—and what remains uncertain

A useful lead, not a complete picture

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