The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Mxra8 is a receptor for multiple arthritogenic alphaviruses
Open accessAbstract
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.
Overview
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.
Integrity signals
Registry
Cites
Statistics
Verification
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.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
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.
Citations
Cites
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
Pushko, P., Pumpens, P., & Grens, E. (2013) · Intervirology · doi:10.1159/000346773 · Cited by 5,975
Improved vectors and genome-wide libraries for CRISPR screening
Sanjana, N. E., Shalem, O., & Zhang, F. (2014) · Nature Methods · doi:10.1038/nmeth.3047 · Cited by 5,239
Genome-scale CRISPR-Cas9 knockout screening in human cells
Shalem, O., Sanjana, N. E., Hartenian, E., Shi, X., Scott, D. A., Mikkelsen, T. S., Heckl, D., Ebert, B. L., Root, D. E., Doench, J. G., et al. (2014) · Science · doi:10.1126/science.1247005 · Cited by 5,234
Li, W., Xu, H., Xiao, T., Cong, L., Love, M. I., Zhang, F., Irizarry, R. A., Liu, J. S., Brown, M., & Liu, X. S. (2014) · Genome Biology · doi:10.1186/s13059-014-0554-4 · Cited by 2,684
RNA-programmed genome editing in human cells
Jinek, M., East, A., Cheng, A., Lin, S., Ma, E., & Doudna, J. (2013) · eLife · doi:10.7554/elife.00471 · Cited by 2,098
Genome-scale CRISPR-Cas9 Knockout and Transcriptional Activation Screening
Joung, J., Konermann, S., Gootenberg, J. S., Abudayyeh, O. O., Platt, R. J., Brigham, M. D., Sanjana, N. E., & Zhang, F. (2017) · Nature Protocols · doi:10.1038/nprot.2017.016 · Cited by 1,243
Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography
Voss, J. E., Vaney, M. C., Duquerroy, S., Vonrhein, C., Girard-Blanc, C., Crublet, E., Thompson, A., Bricogne, G., & Rey, F. A. (2010) · Nature · doi:10.1038/nature09555 · Cited by 696
Junction Adhesion Molecule Is a Receptor for Reovirus
Barton, E. S., Forrest, J. C., Connolly, J. L., Chappell, J. D., Liu, Y., Schnell, F. J., Nusrat, A., Parkos, C. A., & Dermody, T. S. (2001) · Cell · doi:10.1016/s0092-8674(01)00231-8 · Cited by 624
Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus
Oliphant, T., Engle, M. J., Nybakken, G. E., Doane, C., Johnson, S., Huang, L., Gorlatov, S. N., Mehlhop, E., Marri, A., Chung, K. M., et al. (2005) · Nature Medicine · doi:10.1038/nm1240 · Cited by 514
Self-citationAnimal cell mutants defective in glycosaminoglycan biosynthesis.
Esko, J. D., Stewart, T. E., & Taylor, W. H. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.10.3197 · Cited by 513
Akahata, W., Yang, Z., Andersen, H., Sun, S., Holdaway, H. A., Kong, W., Lewis, M. G., Higgs, S., Rossmann, M. G., Rao, S. S., et al. (2010) · Nature Medicine · doi:10.1038/nm.2105 · Cited by 513
Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases
Weaver, S. C., Charlier, C., Vasilakis, N., & Lecuit, M. (2017) · Annual Review of Medicine · doi:10.1146/annurev-med-050715-105122 · Cited by 502
Klimstra, W. B., Ryman, K. D., & Johnston, R. E. (1998) · Journal of Virology · doi:10.1128/jvi.72.9.7357-7366.1998 · Cited by 381
Self-citationHuang, I., Bosch, B., Li, F., Li, W., Lee, K. H., Ghiran, S., Vasilieva, N. Y., Dermody, T. S., Harrison, S. C., Dormitzer, P. R., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508381200 · Cited by 380
Jemielity, S., Wang, J. J., Chan, Y., Ahmed, A. A., Li, W., Monahan, S., Bu, X., Farzan, M., Freeman, G. J., Umetsu, D. T., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003232 · Cited by 377
Structural changes of envelope proteins during alphavirus fusion
Li, L., Jose, J., Xiang, Y., Kuhn, R. J., & Rossmann, M. G. (2010) · Nature · doi:10.1038/nature09546 · Cited by 351
Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus
Pal, P., Dowd, K. A., Brien, J. D., Edeling, M. A., Gorlatov, S. N., Johnson, S., Lee, I. T., Akahata, W., Nabel, G. J., van Duijl-Richter, M. K. S., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003312 · Cited by 301
Self-citationDevelopment of an attenuated strain of chikungunya virus for use in vaccine production
Levitt, N. H., Ramsburg, H. H., Hasty, S. E., Repik, P. M., Cole, F. E., & Lupton, H. W. (1986) · Vaccine · doi:10.1016/0264-410x(86)90003-4 · Cited by 257
Hawman, D. W., Burrack, K. S., Montgomery, S. A., Pal, P., Oko, L. M., Diamond, M., & Morrison, T. E. (2013) · Journal of Virology · doi:10.1128/jvi.02666-13 · Cited by 245
Self-citationBroadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress
Fox, J. M., Long, F., Edeling, M. A., Lin, H., van Duijl-Richter, M. K. S., Fong, R. H., Kahle, K. M., Smit, J. M., Jin, J., Simmons, G., et al. (2015) · Cell · doi:10.1016/j.cell.2015.10.050 · Cited by 223
Self-citationSun, S., Xiang, Y., Akahata, W., Holdaway, H. A., Pal, P., Zhang, X., Diamond, M., Nabel, G. J., & Rossmann, M. G. (2013) · eLife · doi:10.7554/elife.00435 · Cited by 174
Self-citationRose, P. P., Hanna, S. L., Spiridigliozzi, A., Wannissorn, N., Beiting, D. P., Ross, S. R., Hardy, R. W., Bambina, S., Heise, M. T., & Cherry, S. R. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.06.009 · Cited by 165
Smith, S. A., Silva, L. A., Fox, J. M., Flyak, A. I., Kose, N., Sapparapu, G., Khomandiak, S., Ashbrook, A. W., Kahle, K. M., Fong, R. H., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.06.009 · Cited by 143
Self-citationPropagation, Quantification, Detection, and Storage of West Nile Virus
Brien, J. D., Lazear, H. M., & Diamond, M. (2013) · Current Protocols in Microbiology · doi:10.1002/9780471729259.mc15d03s31 · Cited by 120
Self-citationGardner, C. L., Burke, C. W., Higgs, S., Klimstra, W. B., & Ryman, K. D. (2012) · Virology · doi:10.1016/j.virol.2011.12.020 · Cited by 113
Self-citationChikungunya virus pathogenesis: From bedside to bench
Couderc, T., & Lecuit, M. (2015) · Antiviral Research · doi:10.1016/j.antiviral.2015.07.002 · Cited by 111
Selvarajah, S., Sexton, N. R., Kahle, K. M., Fong, R. H., Mattia, K.-A., Gardner, J., Lü, K., Liss, N. M., Salvador, B., Tucker, D. F., et al. (2013) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002423 · Cited by 110
Self-citationJin, J., Liss, N. M., Chen, D.-H., Liao, M., Fox, J. M., Shimak, R. M. K., Fong, R. H., Chafets, D. M., Bakkour, S., Keating, S. M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.11.043 · Cited by 107
Self-citationAshbrook, A. W., Burrack, K. S., Silva, L. A., Montgomery, S. A., Heise, M. T., Morrison, T. E., & Dermody, T. S. (2014) · Journal of Virology · doi:10.1128/jvi.01672-14 · Cited by 102
Taube, S., Rubin, J. R., Katpally, U., Smith, T. J., Kendall, A., Stuckey, J. A., & Wobus, C. E. (2010) · Journal of Virology · doi:10.1128/jvi.00316-10 · Cited by 84
Chemokine receptors as fusion cofactors for human immunodeficiency virus type 1 (HIV-1)
Doranz, B. J., Berson, J. F., Rucker, J. B., & Doms, R. W. (1997) · Immunologic Research · doi:10.1007/bf02786321 · Cited by 82
Self-citationLee, J., Nyenhuis, D. A., Nelson, E. A., Cafiso, D. S., White, J. M., & Tamm, L. K. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1708052114 · Cited by 69
Yonezawa, T., Ohtsuka, A., Yoshitaka, T., Hirano, S., Nomoto, H., Yamamoto, K., & Ninomiya, Y. (2003) · Glia · doi:10.1002/glia.10279 · Cited by 55
DICAM inhibits angiogenesis via suppression of AKT and p38 MAP kinase signalling
Han, S. W., Jung, Y., Lee, E., Park, H., Kim, G.-W., Jeong, J., Han, M. S., & Choi, J. (2013) · Cardiovascular Research · doi:10.1093/cvr/cvt019 · Cited by 47
DICAM inhibits osteoclast differentiation through attenuation of the integrin αVβ3 pathway
Jung, Y., Han, S. W., Kim, G.-W., Jeong, J., Kim, H., & Choi, J. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1632 · Cited by 46
Jung, Y., Jin, J., Jeong, J., Kim, H., Park, N. R., & Choi, J. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21438 · Cited by 36
Loh, J., Zhao, G., Nelson, C. A., Coder, P., Droit, L., Handley, S. A., Johnson, L. S., Vachharajani, P., Guzmán, H., Tesh, R. B., et al. (2011) · Journal of Virology · doi:10.1128/jvi.01661-10 · Cited by 26
Self-citationLee, J., Nyenhuis, D. A., Nelson, E. A., Cafiso, D. S., White, J. M., & Tamm, L. K. (2017) · Biophysical Journal · doi:10.1016/j.bpj.2016.11.468 · Cited by 25
Alphavirus Entry into Host Cells
Vancini, R. G., Hernandez, R. G., & Brown, D. T. (2014) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2014.10.002 · Cited by 21
Rodent Herpesvirus Peru Encodes a Secreted Chemokine Decoy Receptor
Lubman, O., Cella, M., Wang, X., Monte, K. J., Lenschow, D. J., Huang, Y. H., & Fremont, D. H. (2013) · Journal of Virology · doi:10.1128/jvi.02729-13 · Cited by 16
Self-citation
Cited by
Sorted by citations
Bartholomeeusen, K., Daniel, M., LaBeaud, A. D., Gasque, P., Peeling, R. W. W., Stephenson, K. E., Ng, L. F. P., & Ariën, K. K. (2023) · Nature Reviews Disease Primers · doi:10.1038/s41572-023-00429-2 · Cited by 345
A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry
Zhu, Y., Feng, F., Hu, G., Wang, Y., Yin, Y., Zhu, Y., Xü, W., Cai, X., Sun, Z., Han, W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21213-4 · Cited by 307
Self-citationA Review on Chikungunya Virus Epidemiology, Pathogenesis and Current Vaccine Development
Cavalcanti, T. Y. V. D. L., Pereira, M. R., de Paula, S. O., & França, R. F. D. O. (2022) · Viruses · doi:10.3390/v14050969 · Cited by 284
Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor
Basore, K., Kim, A. S., Nelson, C. A., Zhang, R., Smith, B. K., Uranga, C., Vang, L., Cheng, M., Gross, M. L., Smith, J. D., et al. (2019) · Cell · doi:10.1016/j.cell.2019.04.006 · Cited by 209
Self-citationRheumatic manifestations of chikungunya: emerging concepts and interventions
Suhrbier, A. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0276-9 · Cited by 210
Metadata
- 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.
- ORCID
- Venue
- Nature
- Published
- 2018-05
- Volume
- 557
- Issue
- 7706
- Pages
- 570-574
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5970976
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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
