|Van Heerden, J|
|Rieder, Aida - Elizabeth|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 11/1/2006
Publication Date: 11/26/2006
Citation: Maree, F.F., Blignaut, B., Van Heerden, J., Vosloo, W., Theron, J., Rieder, A.E. 2006. Selection of Variants Utilizing Heparin Sulphate For Cell Entry When South African Territories Foot-and-Mouth Disease Virus is Adapted for Growth on Cell Culture. European Study Group on the Molecular Biology of Picornaviruses (EUROPIC) 2006 Meeting, page F14. Interpretive Summary:
Technical Abstract: Foot-and-mouth disease virus (FMDV) attains entry to epithelial cells by affinity for at least four members of the integrin family of receptors. Adaptation of field isolates to grow in cultured cells is an essential step towards development of vaccines against new outbreak strains. This is made possible by the virus acquiring the capacity to bind to cell-surface heparin sulphate proteoglycans (HSPG) on repeated passage in cell culture. Although biding of the virus to integrins with HSPG involve a conserved RGD sequence located within the G-H loop of 1D, the interaction with HSPG is currently not defined. The binding site for HSPG is a shallow depression on the virion surface, located at the junction of the three major capsid proteins. Unlike type A viruses, a SAT1 virus adapted on cell culture presented with an accumulation of positively charged residues (H, K or R) at positions 136 to 138 of 1D, which predicted from the 3-dimensional structure is positioned within the HSPG binding depression on the virion surface. These positively charged residues are absent in the SAT1 field isolate that utilizes mainly the integrin receptors. To improve our understanding whether the ability of the SAT types to acquire HSPG binding is via the described surface depression we have further investigated SAT1 and SAT2 viruses adapted on cell culture with the ability to replicate in CHO-K1 cells. The group also compared the particle disassembly of a SAT2 virus, SIM/7/83, in acid and high ionic-strength environments with high affinity heparin sulphate binding properties.