Integrin alphavbeta1 promotes infection by human metapneumovirus.
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 alphavbeta1 integrin inhibit infectivity of hMPV but not RSV. Transfection of nonpermissive cells with alphav or beta1 cDNAs confers hMPV infectivity, whereas reduction of alphav and beta1 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 alphavbeta1 integrin is a functional receptor for hMPV.
Cseke
Gabriella
G
Department of Chemistry, Vanderbilt University College of Arts and Sciences, Nashville, TN 37232, USA.
Maginnis
Melissa S
MS
Cox
Reagan G
RG
Tollefson
Sharon J
SJ
Podsiad
Amy B
AB
Wright
David W
DW
Dermody
Terence S
TS
Williams
John V
JV
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D006801:Humans; D029121:Metapneumovirus / Q000276:immunology / Q000472:pathogenicity*; D034741:RNA, Small Interfering; D019030:Receptors, Vitronectin / Q000276:immunology / Q000502:physiology*; D013552:Swine; D014162:Transfection; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000502:physiology; D014774:Virulence / Q000502:physiology*
D000914:Antibodies, Viral; D034741:RNA, Small Interfering; D019030:Receptors, Vitronectin; D014760:Viral Fusion Proteins; C094340:integrin alphavbeta1