Alpha4beta1 integrin acts as a cell receptor for murine polyomavirus at the postattachment level.
The initial interaction of murine polyomavirus (Py) with host cells occurs through direct binding of the major capsid protein VP1 with cell membrane molecules containing terminal sialic acids; however, these Py receptor molecules have not yet been identified. Analysis of the capsid protein primary sequences of all murine strains revealed the presence of integrin ligand motifs in the DE and EF loops of VP1 (LDV and DLXXL, respectively) and at the N terminus of VP2 (DGE). We show that infectivity of the Py A2 strain in mouse Swiss 3T3 fibroblasts is significantly reduced only in the presence of natural integrin ligands carrying an LDV motif or antibodies directed against the alpha4 and beta1 integrin subunits. Furthermore, we demonstrate that expression of the alpha4 subunit in the alpha4-deficient BALB/c 3T3 cells increases viral infectivity. Addition of alpha4 function-blocking antibodies, prior to or after virus adsorption, blocks this increased infectivity without affecting virus binding to cells. Taken together, these data indicate that expression of alpha4 integrin enhances permissivity to Py, probably by acting as one of the postattachment receptors.
Caruso
Maddalena
M
Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Istituto Pasteur-Fondazione Cenci Bolognetti, Università di Roma La Sapienza, Rome, Italy.
Belloni
Laura
L
Sthandier
Olga
O
Amati
Paolo
P
Garcia
Marie-Isabelle
MI
D016475:3T3 Cells; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D036022:Capsid Proteins / Q000235:genetics / Q000502:physiology; D039041:Integrin alpha4beta1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D011120:Polyomavirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D012794:Sialic Acids / Q000737:chemistry
D036022:Capsid Proteins; D039041:Integrin alpha4beta1; D008024:Ligands; D011991:Receptors, Virus; D012794:Sialic Acids; C062481:VP1 protein, polyomavirus