Henipavirus Receptor Identified Nipah Virus

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Henipavirus Receptor Identified Nipah Virus

RESEARCH HIGHLIGHTS URLs Ephrin B2: http://us.expasy.org/ VIROLOGY uniprot/Q5JV56 Hendra virus: http://www.ncbi.nlm. nih.gov/genomes/framik. cgi?db=genome&gi=13716 Henipavirus receptor identified Nipah virus: http://www.ncbi.nlm. nih.gov/genomes/framik. cgi?db=genome&gi=15627 Ephrin B2, a member of the ephrin using two different approaches, the ther analysis, and cell-fusion assays receptor tyrosine kinase family, has identity of this receptor has been identified human ephrin B2 as the been identified as the cell-surface revealed. receptor for both Hendra virus and receptor for Hendra virus and Nipah Negrete et al. identified the Nipah virus, extending the findings virus. receptor for Nipah virus by immu- of Negrete et al. Bonaparte et al. went Hendra virus and Nipah virus noprecipitating permissive and on to use live-virus-infection assays are members of the new genus non-permissive cell lines using the of human and primate cells to con- Henipavirus in the Paramyxoviridae ectodomain of the Nipah virus G firm that in vivo, henipavirus infec- family. Both viruses have an unusu- protein fused to the Fc region of tion occurs through ephrin B2. ally broad species tropism, encom- human IgG1 as bait. The immuno- The identification of the receptor passing many mammals, including precipitation identified a 48-kDa is a huge breakthrough for research- humans, horses, pigs, cats, dogs and membrane protein, and subsequent ers working on these emerging fruit bats. It had previously been trypsin digestion and mass-spec- viruses, and will hopefully aid efforts shown that henipaviruses attach to trometry analysis identified the to understand their pathogenesis and and enter host cells using their fusion protein as human ephrin B2. Further facilitate the development of effective (F) and attachment (G) cell-surface cell-based experiments demonstrated therapies. glycoproteins, and the cell-surface that ephrin B2 is required for the Sheilagh Molloy receptor for both viruses had been formation of endothelial syncytia, a References and links shown to be protease sensitive. Now, characteristic of Nipah virus infec- ORIGINAL RESEARCH PAPERS Bonaparte, M. L. et al. Ephrin-B2 ligand is a functional receptor tion. Finally, recombinant vesicular for Hendra virus and Nipah virus. Proc. Natl Acad. stomatitis virus pseudotyped with Sci. USA 5 July 2005 (doi:10.1073/ pnas.0504887102) | Negrete, O. A. et al. EphrinB2 the Nipah virus F and G proteins is the entry receptor for Nipah virus, an emergent was shown to require ephrin B2 for deadly paramyxovirus. Nature 6 July 2005 cell entry. (doi:10.1038/nature03838) Bonaparte et al. used a microar- ray approach in their work to iden- tify the receptor for both members of the Henipavirus genus. Previous work by this group had identified a human cell line that is non-permissive for henipavirus fusion and infection, and mRNA from this cell line and three permissive cell lines was used in an Affymetrix gene chip analysis to screen for genes that were differentially expressed. Based on prior observations, 21 candidate receptor genes that encode membrane-expressed proteins of the expected size range were identified. Ten candidates were chosen for fur- NATURE REVIEWS | MICROBIOLOGY VOLUME 3 | SEPTEMBER 2005 | 1 © 2005 Nature Publishing Group .

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