Vitronectin receptors, alpha v integrins, are recognized by several non-RGD-containing echoviruses in a continuous laboratory cell line and also in primary human Langerhans' islets and endothelial cells.
Previously published data suggest that the RGD-recognizing integrin, alphavbeta3, known as the vitronectin receptor, acts as a cellular receptor for RGD-containing enteroviruses, coxsackievirus A9 (CAV-9) and echovirus 9 (E-9), in several continuous cell lines as well as in primary human Langerhans' islets. As this receptor is also capable of binding the ligands by a non-RGD-dependent mechanism, we investigated whether vitronectin receptors, alpha v integrins, might act as receptors for other echoviruses that do not have the RGD motif. Blocking experiments with polyclonal anti-alphavbeta3 antibody showed that both primary human islets and a continuous laboratory cell line of green monkey kidney origin (GMK) are protected similarly from the adverse effects of several non-RGD-containing echovirus (E-7, -11, -25, -30, -32) infections. In contrast, corresponding studies on primary human endothelial cells showed that the receptor works only for E-25, E-30, E-32 and CAV-9. The inhibitory effect of the antibody was not restricted to prototype strains of echoviruses, as GMK cells infected with several field isolates of the corresponding serotypes were also protected from virus-induced cytopathic effects. Co-localization of virus particles with the receptor molecules in both GMK and primary human endothelial cells was demonstrated by live-cell stainings and confocal microscopy. Remarkably, in spite of similar virus-receptor co-localization and a comparable protective effect of the alphavbeta3 antibody, the entry pathways of the studied virus strains seemed to be divergent.
National Institute for Health and Welfare, Helsinki, Finland.
Petri
P
Ylipaasto
Mervi
M
Eskelinen
Kaija
K
Salmela
Tapani
T
Hovi
Merja
M
Roivainen
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D042783:Endothelial Cells / Q000821:virology*; D029822:Enterovirus B, Human / Q000502:physiology*; D006801:Humans; D039564:Integrin alphaV / Q000502:physiology*; D007515:Islets of Langerhans / Q000821:virology*; D018613:Microscopy, Confocal; D011991:Receptors, Virus / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000502:physiology*; D053585:Virus Attachment
D039564:Integrin alphaV; D011991:Receptors, Virus; D019030:Receptors, Vitronectin