|Maree, Francois - ONDERSTEPOORT VET INST|
Submitted to: Keystone Symposia
Publication Type: Abstract Only
Publication Acceptance Date: February 2, 2006
Publication Date: February 24, 2006
Citation: Maree, F.F., Aschenbrenner, L.M., Baxt, B., Rieder, A.E. 2006. Analysis of the receptor usage and growth determinants of outbreak and vaccine strains of south african territories of foot-and-mouth disease virus. Keystone Symposia. 2006. P. 74. Technical Abstract: Foot and mouth disease (FMD) is an economically important disease that affects cloven-hoofed animals and leads to production losses, especially in intensive farming systems. The etiologic agent, FMD virus (FMDV) is a single stranded, positive sense RNA virus of the genus Aphthovirus of the Picomaviridae. FMDV relies on binding to the cell surface via a conserved RGD sequence located within a flexible external loop between the G and H strands of viral protein 1 (VP1) for cell entry. At least four members of the integrin family of receptors, alpha v beta 1,alpha v beta 3,alpha v beta 6, alpha v beta 8, and heparan-sulphate receptors have been identified as receptors for FMDV in vitro. Although our understanding of the events during viral entry into the infected cell is still limited, V. O'Donnell et al.(2005) recently demonstrated that FMDV utilizes the clathrin-mediated endocytosis pathway to infect cells. Viral replication is then initiated due to acidification of endocytic vesicles, causing the breakdown of the viral capsid and release of the genome. In this study, we have investigated the three South African Territories(SAT) type viruses, prevalent in sub-Saharan Africa, for receptor preference and found high affinity for the bovine alpha V beta 6 integrin receptors and heparin-sulphate receptors for BHK adapted viruses. Genetically engineered infectious cDNA clones corresponding to the parental and cell-adapted SAT1/SAR/9/81 were generated and in vitro characterized. Viable virus recovered from the genome-length clone displayed a variant small plaque phenotype of the tissue culture adapted SAR/9/81 virus. At the genotypic level, four amino acid changes were observed including the C-terminal region of VP3 and the N-terminal of VP1 coding regions, one of which add a positive charged lysine residue to VP1. The alteration in cell-receptor usage was accompanied by differences in the stability of the particles derived from the cell-adapted viruses in comparison to the parental SAT1/SAR/9/81 isolated from impala epithelium.