ABSTRACT
We have previously reported that Foot-and-mouth disease virus (FMDV), which is virulent for cattle and swine, can utilize the integrin αvβ3 as a receptor on cultured cells. Since those studies were performed with the human integrin, we have molecularly cloned the bovine homolog of the integrin αvβ3 and have compared the two receptors for utilization by FMDV. Both the αv and β3subunits of the bovine integrin have high degrees of amino acid sequence similarity to their corresponding human subunits in the ectodomains (96%) and essentially identical transmembrane and cytoplasmic domains. Within the putative ligand-binding domains, the bovine and human αv subunits have a 98.8% amino acid sequence similarity while there is only a 93% similarity between the β3 subunits of these two species. COS cell cultures, which are not susceptible to FMDV infection, become susceptible if cotransfected with αv and β3 subunit cDNAs from a bovine or human source. Cultures cotransfected with the bovine αvβ3 subunit cDNAs and infected with FMDV synthesize greater amounts of viral proteins than do infected cultures cotransfected with the human integrin subunits. Cells cotransfected with a bovine αv subunit and a human β3subunit synthesize viral proteins at levels equivalent to those in cells expressing both human subunits. However, cells cotransfected with the human αv and the bovine β3 subunits synthesize amounts of viral proteins equivalent to those in cells expressing both bovine subunits, indicating that the bovine β3 subunit is responsible for the increased effectiveness of this receptor. By engineering chimeric bovine-human β3subunits, we have shown that this increase in receptor efficiency is due to sequences encoding the C-terminal one-third of the subunit ectodomain, which contains a highly structured cysteine-rich repeat region. We postulate that amino acid sequence differences within this region may be responsible for structural differences between the human and bovine β3 subunit, leading to more efficient utilization of the bovine receptor by this bovine pathogen.
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