Integrin αvβ1 promotes infection by human metapneumovirus

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 5; pp. 1566 - 1571
• Main Authors: Cseke, Gabriella, Maginnis, Melissa S, Cox, Reagan G, Tollefson, Sharon J, Podsiad, Amy B, Wright, David W, Dermody, Terence S, Williams, John V
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences 2009
• Subjects: adults; amino acid sequences; antibodies; cations; CD29 antigen; chelating agents; children; complementary DNA; EDTA (chelating agent); glycoproteins; human diseases; Human metapneumovirus; pathogenicity; respiratory tract diseases; small interfering RNA; transfection; viruses
• ISSN: 0027-8424; 1091-6490

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.