Cited by 448Mosquito-borne diseases and controlViral Infections and VectorsSARS-CoV-2 and COVID-19 Research

Mxra8 is a receptor for multiple arthritogenic alphaviruses

Open access
Zhang, Rong, Kim, Arthur S., Fox, Julie M., Nair, Sharmila, Basore, Katherine, Klimstra, William B., Rimkunas, Rebecca, Fong, Rachel H. +6 more·2018·Nature

Abstract

Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease 1 . The host factors required for alphavirus entry remain poorly characterized 2 . Here we use a genome-wide CRISPR-Cas9-based screen to identify the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses, including chikungunya, Ross River, Mayaro and O'nyong nyong viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced levels of viral infection of cells and, reciprocally, ectopic expression of these genes resulted in increased infection. Mxra8 bound directly to chikungunya virus particles and enhanced virus attachment and internalization into cells. Consistent with these findings, Mxra8-Fc fusion protein or anti-Mxra8 monoclonal antibodies blocked chikungunya virus infection in multiple cell types, including primary human synovial fibroblasts, osteoblasts, chondrocytes and skeletal muscle cells. Mutagenesis experiments suggest that Mxra8 binds to a surface-exposed region across the A and B domains of chikungunya virus E2 protein, which are a speculated site of attachment. Finally, administration of the Mxra8-Fc protein or anti-Mxra8 blocking antibodies to mice reduced chikungunya and O'nyong nyong virus infection as well as associated foot swelling. Pharmacological targeting of Mxra8 could form a strategy for mitigating infection and disease by multiple arthritogenic alphaviruses.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41586-018-0121-3

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Sample sizes were determined based on previous in vivo virus challenge experiments.

    “sample sizes were determined based on previous in vivo virus challenge experiments4.”

    From LDLRAD3 is a receptor for Venezuelan equine encephalitis virus (2020) · cites this paper as [4]

    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)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. [21]Sun S Structural analyses at pseudo atomic resolution of Chikungunya virus antibody neutralization mechanisms eLife 2 e00435 2013 23577234 PMC3614025

Cited by

Sorted by citations

Authors
Zhang, R., Kim, A. S., Fox, J. M., Nair, S., Basore, K., Klimstra, W. B., Rimkunas, R., Fong, R. H., Lin, H., Poddar, S., Crowe, J. E., Doranz, B. J., Fremont, D. H., & Diamond, M. S.
Affiliations
  • Washington University in St. Louis (US)
  • University of Pittsburgh (US)
  • Integral Molecular (United States) (US)
  • Vanderbilt University Medical Center (US)
Corresponding author
Diamond, Michael S.
Venue
Nature
Published
2018-05
Volume
557
Issue
7706
Pages
570-574
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2803841447
Cited by
448
References
41
Citations by year
2026: 60 · 2025: 61 · 2024: 58 · 2023: 54 · 2022: 64 · 2021: 62 · 2020: 47 · 2019: 35 · 2018: 6
FWCI
38.14
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI114816, R01AI123348, R01AI095436)
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 › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
MXRA8, arthritogenic alphaviruses, chikungunya virus, Ross River virus, Mayaro virus, O'nyong-nyong virus, viral entry, adhesion molecules, foot swelling, synovial fibroblasts, CRISPR-Cas9 screen
MeSH terms
Animals, Chikungunya virus, Fibroblasts, Humans, Immunoglobulins, Male, Membrane Proteins, Osteoblasts, Receptors, Fc, Receptors, Virus, 3T3 Cells, Muscle, Skeletal, Antibodies, Blocking, Chondrocytes, Mice, CRISPR-Cas Systems, O'nyong-nyong Virus

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review