|Rieder, Aida - Elizabeth|
Submitted to: Virus Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/9/2010
Publication Date: 12/15/2010
Citation: Maree, F.F., Blignaut, B., Aschenbrenner, L., Burrage, T., Rieder, A.E. 2010. Analysis of sat type foot-and-mouth disease virus capsid proteins: influence of receptor usage on the properties of virus particles. Virus Research. 155:462-472. Interpretive Summary: As a first step towards understanding virus-host interaction and pathogenic mechanisms of the South African Territories (SAT) foot-and-mouth disease viruses (FMDV), infectious cDNA clones were constructed for the three seorotypes of SAT viruses , SAT1, SAT2 and SAT3. We found that the vaccine viruses, which have been adapted to tissue culture, utilized a different, other than natural receptor, for cell entry. Those viruses that use alternative receptors showed a higher tendency to form aggregates and slightly better stability under different environmental conditions. The information obtained in this study could aid in the rational design of engineered vaccine candidates for the control of FMD.
Technical Abstract: The viral mechanism involved in foot-and-mouth disease (FMD) tissue tropism, host range and the events during viral entry into susceptible cells is not well understood. Using infectious cDNA clones of the three South African Territories (SAT) type viruses prevalent in sub-Saharan Africa, the biological and genetic properties of field isolates and laboratory strains were examined. Viable virus derived from the tissue culture-adapted SAT1/SAR/9/81 (vSAT1tc) genome-length clone displayed a small plaque phenotype. At the genotypic level, four amino acid residues (VP3 Asp192->Tyr; VP3 Ser217->Iso; VP1 Ala69->Gly and VP1 Asn110->Lys) in the capsid of the tissue culture-adapted virus differed from the impala epithelium strain, one of which added a positively-charged lysine residue to VP1. Furthermore, the vSAT1tc virus displayed a high affinity for heparan sulphate proteoglycan (HSPG) receptors while SAT1, SAT2 and SAT3 field strains relied strongly on alpha V beta 6 integrin receptors for cell entry. Acquisition of HSPG-receptor usage of the cell-adapted viruses was accompanied by differences in particle aggregation and slight differences in acid stability, without altering the overall antigenic features. Thus, acquisition of HSPG binding may be beneficial for adaptation of SAT type field strains to cell culture, while limiting the spread of this highly contagious virus in livestock.