Integrin αvβ1 promotes infection by human metapneumovirus

doi:10.1073/pnas.0801433106

Integrin αvβ1 promotes infection by human metapneumovirus

^aDepartment of Chemistry, Vanderbilt University College of Arts and Sciences, Nashville, TN 37232; and
Departments of ^bMicrobiology and Immunology and
^cPediatrics and
^dElizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN 37232

Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved December 15, 2008
↵¹G.C., M.S.M., and R.G.C. contributed equally to this work. (received for review February 14, 2008)

Abstract

Human metapneumovirus (hMPV) is a recently described paramyxovirus that causes lower respiratory infections in children and adults worldwide. The hMPV fusion (F) protein is a membrane-anchored glycoprotein and major protective antigen. All hMPV F protein sequences determined to date contain an Arg-Gly-Asp (RGD) sequence, suggesting that F engages RGD-binding integrins to mediate cell entry. The divalent cation chelator EDTA, which disrupts heterodimeric integrin interactions, inhibits infectivity of hMPV but not the closely related respiratory syncytial virus (RSV), which lacks an RGD motif. Function-blocking antibodies specific for αvβ1 integrin inhibit infectivity of hMPV but not RSV. Transfection of nonpermissive cells with αv or β1 cDNAs confers hMPV infectivity, whereas reduction of αv and β1 integrin expression by siRNA inhibits hMPV infection. Recombinant hMPV F protein binds to cells, whereas Arg-Gly-Glu (RGE)-mutant F protein does not. These data suggest that αvβ1 integrin is a functional receptor for hMPV.

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Footnotes

²To whom correspondence should be addressed. E-mail: john.williams{at}vanderbilt.edu
Author contributions: G.C., M.S.M., R.G.C., D.W.W., T.S.D., and J.V.W. designed research; G.C., M.S.M., R.G.C., S.J.T., and A.B.P. performed research; G.C., M.S.M., R.G.C., D.W.W., T.S.D., and J.V.W. analyzed data; and G.C., M.S.M., R.G.C., D.W.W., T.S.D., and J.V.W. wrote the paper.
Conflict of interest statement: Dr. Williams has served as a one-time consultant for Med-Immune, Inc.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0801433106/DCSupplemental.
Freely available online through the PNAS open access option.