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PNAS 102 (30): 10652-10657

Copyright © 2005 by the National Academy of Sciences.

From The Cover

MICROBIOLOGY

Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus

Matthew I. Bonaparte * {dagger}, Antony S. Dimitrov * {dagger}, Katharine N. Bossart {dagger}, {ddagger}, Gary Crameri {ddagger}, Bruce A. Mungall {ddagger}, Kimberly A. Bishop *, Vidita Choudhry §, Dimiter S. Dimitrov §, Lin-Fa Wang {ddagger}, Bryan T. Eaton {ddagger}, and Christopher C. Broder *, ¶

*Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814; {ddagger}Commonwealth Scientific and Industrial Research Organization Livestock Industries, Australian Animal Health Laboratory, Geelong, Victoria 3220, Australia; and §Protein Interactions Group, Laboratory of Experimental and Computational Biology, National Cancer Institute, National Institutes of Health, Frederick, MD 21702

Communicated by Bernard Moss, National Institutes of Health, Bethesda, MD, June 10, 2005

Received for publication June 3, 2005.

Abstract: Hendra virus (HeV) and Nipah virus (NiV) belong to the genus Henipavirus of the family Paramyxoviridae and are unique in that they exhibit a broad species tropism and cause fatal disease in both animals and humans. They infect cells through a pH-independent membrane fusion process mediated by their fusion and attachment glycoproteins. Previously, we demonstrated identical cell fusion tropisms for HeV and NiV and the protease-sensitive nature of their unknown cell receptor and identified a human cell line (HeLa-USU) that was nonpermissive for fusion and virus infection. Here, a microarray analysis was performed on the HeLa-USU cells, permissive HeLa-CCL2 cells, and two other permissive human cell lines. From this analysis, we identified a list of genes encoding known and predicted plasma membrane surface-expressed proteins that were highly expressed in all permissive cells and absent from the HeLa-USU cells and rank-ordered them based on their relative levels. Available expression vectors containing the first 10 genes were obtained and individually transfected into HeLa-USU cells. One clone, encoding human ephrin-B2 (EFNB2), was found capable of rendering HeLa-USU cells permissive for HeV- and NiV-mediated cell fusion as well as infection by live virus. A soluble recombinant EFNB2 could potently block fusion and infection and bind soluble recombinant HeV and NiV attachment glycoproteins with high affinity. Together, these data indicate that EFNB2 serves as a functional receptor for both HeV and NiV. The highly conserved nature of EFNB2 in humans and animals is consistent with the broad tropism exhibited by these emerging zoonotic viruses.

Freely available online through the PNAS open access option.

Abbreviations: EFNB2, ephrin-B2; F, fusion glycoprotein; G, attachment glycoprotein; sG, soluble G; Pab, polyclonal antibody; HeV, Hendra virus; NiV, Nipah virus; TCID50, tissue culture 50% infective dose.

{dagger} M.I.B., A.S.D., and K.N.B. contributed equally to this work.

To whom correspondence should be addressed. E-mail: cbroder{at}usuhs.mil.

© 2005 by The National Academy of Sciences of the USA

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