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Title: Mapping of amino acid residues responsible for adhesion of cell culture-adapted foot-and-mouth disease SAT type viruses

Author
item MAREE, FRANCOIS - Onderstepoort Veterinary Institute
item BLIGNAUT, BELINDS - University Of Pretoria
item DE BEER, TJAART - University Of Pretoria
item VISSER, NICO - Intervet - Netherlands
item Rieder, Aida - Elizabeth

Submitted to: Virus Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/8/2010
Publication Date: 10/1/2011
Citation: Maree, F.F., Blignaut, B., De Beer, T.A., Visser, N., Rieder, A.E. 2011. Mapping of amino acid residues responsible for adhesion of cell culture-adapted foot-and-mouth disease SAT type viruses. Virus Research. 153(1):82-91.

Interpretive Summary: In this report novel amino acid residues within the capsid proteins of Foot-and-Mouth Disease Virus (FMDV) South African Territories (SAT)serotype 1 and SAT serotype 2 viruses were identified that affect virus host range in cell culture and plaque phenotype. We demonstrated that cell culture adaptation phenotype is acquired following repeated passages of the field strains in cell cultures. Furthermore, we illustrated that this phenotype can be transferred to an infectious copy DNA (cDNA) clone of FMDV field strains from which viable cell culture adapted viruses were recovered. This information is valuable for understanding the mechanism of FMDV adaptation to the host cell in vitro and the identification of amino acid in the 9outer capsid region reponsible for binding to heparan sulfate psoteoglycan (HSPG).

Technical Abstract: Foot-and-mouth disease virus (FMDV) infects host cells by adhering to the alpha v subgroup of the integrin family of cellular receptors in a arginine-glycine-aspartic acid (RGD)-dependent manner. FMD viruses, propagated in non-host cell cultures are reported to acquire the ability to enter cells via alternative cell surface molecules. Sequencing analysis of South African Territories (SAT) serotype 1 and serotype 2 (SAT1 and SAT2) cell culture-adapted variants showed acquisition of positively-charged amino acid residues within surface-exposed loops of the outer capsid structural proteins. The fixation of positively-charged residues at position 110-112 in the beta F- beta G loop of VP1 of SAT1 isolates is thought to correlate with the acquisition of the ability to utilise alternative glycosaminoglycan (GAG) molecules for cell entry. A similar surface-exposed viral protein 1 (VP1) loop, prone to accumulate positively-charged residues in SAT2 viruses, was mapped to residues 83-85 of VP1. Both regions surround the five-fold axis of the virion and are required to establish an efficient infection in cultured cells. Recombinant viruses containing these changes as single substitutions were able to infect hampster overic cell line - k1 (CHO-K1), which expresses GAG, cells and demonstrated increased infectivity in baby hamster kidney (BHK-21) cells. Therefore, recombinant SAT viruses engineered to express substitutions that induce GAG-binding could be exploited in the rational design of vaccine seed stock with improved growth properties in cell cultures.