Involvement of beta2-microglobulin and integrin alphavbeta3 molecules in the coxsackievirus A9 infectious cycle.

It is becoming apparent that many viruses employ more than one cell surface molecule for their attachment and cell entry. In this study, we have tested the role of integrin alpha(v)beta3 and MHC class I molecules in the coxsackievirus A9 (CAV-9) infectious cycle. Binding experiments utilizing CHO cells transfected and expressing human integrin alpha(v)beta3, revealed that CAV-9 particles were able to bind to cells, but did not initiate a productive cell infection. Antibodies specific for integrin alpha(v)beta3 molecules significantly reduced CAV-9 infection in susceptible cell lines. Moreover, MAbs specific for beta2-microglobulin (beta2-m) and MHC class I molecules completely inhibited CAV-9 infection. To assess the effect of these antibodies on virus binding, we analysed CAV-9 binding by flow cytometry in the presence of alpha2-m- or integrin alpha(v)beta3-specific antibodies. The results showed a reduction in CAV-9 binding in the presence of integrin alpha(v)beta3-specific antibodies while there was no reduction in the presence of beta2-m-specific MAb. Taken together, these data suggest that integrin alphavbeta3 is required for CAV-9 attachment but is not sufficient for cell entry, while beta2-m, although not directly involved in CAV-9 binding, plays a post-attachment role in the CAV-9 infectious process, possibly being involved in virus entry.