Foot-and-mouth disease virus can utilize the C-terminal extension of coxsackievirus A9 VP1 for cell infection.
Foot-and-mouth disease virus (FMDV) is known to employ the conserved Arg-Gly-Asp (RGD) tripeptide located on the variable betaG-betaH loop of the VP1 capsid protein for binding to cells. Coxsackievirus A9 (CAV9) also carries an RGD sequence, but on a short C-terminal extension of its VP1 and in a different amino acid context. This apparent relationship raised the question of whether insertion of the heterologous CAV9 sequence into FMDV would influence infection by the genetically modified FMDV. Four VP1 mutants were generated by PCR mutagenesis of a full-length FMDV cDNA plasmid. After transfection of BHK-21 cells, viral protein synthesis and virus particle formation could be detected. Two of the four mutants, mV9b and mV9d, could be propagated in BHK-21 cells, but not in CV-1 cells. Both of these mutants contained 17 amino acids of the C terminus of CAV9 VP1. Infection of BHK cells could be specifically inhibited by rabbit immune serum raised against a synthetic peptide representing the amino acid sequence of the C-terminal extension of CAV9 VP1. This demonstrated the direct involvement of the inserted sequence in cell infection. In fact, genetically modified FMDV O(1)K was capable of employing the VP1 C-terminal RGD region of CAV9 for infection of BHK cells. In addition, these results show that, even in cell culture-adapted viruses, the RGD-containing betaG-betaH loop plays an important role in virus infectivity.
Leippert
Martina
M
Federal Research Centre for Animal Virus Diseases, Paul-Ehrlich-Strasse 28, D-72076 Tübingen, Germany1.
Pfaff
Eberhard
E
Federal Research Centre for Animal Virus Diseases, Paul-Ehrlich-Strasse 28, D-72076 Tübingen, Germany1.
D000595:Amino Acid Sequence; D000818:Animals; D005537:Aphthovirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002213:Capsid / Q000235:genetics; D036022:Capsid Proteins; D002460:Cell Line; D004770:Enterovirus / Q000737:chemistry / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D013045:Species Specificity; D014162:Transfection; D014774:Virulence
D036022:Capsid Proteins; C442501:VP1 protein, Foot-and-mouth disease virus