No description available.

No description available.

Infection of animal cells with picornaviruses results in the accumulation of replication associated membrane bound vesicles and a cessation in the trafficking of integral membrane and secreted proteins. At present little is known about the role of Foot-and-mouth disease virus (FMDV) non-structural proteins in infection, or on trafficking events in cells. In this study we utilise state-of-the-art bioimaging technology and fluorescent protein chimeras to ascertain the effects of expressing FMDV non-structural proteins 2B, 2C, 2BC, 3A and 3AB on cellular organelles, and on the trafficking of vesicular stomatitis virus glycoprotein (VSVG). The expression of protein 2C in cells resulted in a membrane bound reticular distribution that appeared to form novel structures juxtaposing the cell nucleus. In 2C positive cells these novel structures co-distributed with the ER markers ERp60 and DsRedER. The formation of GFP-2C positive structures was visualised in live cells using wide-field microscopy showing structures forming from the peripheral reticular distribution and migrating towards the nucleus. The putative role of microtubules in the formation and movement of these structures was suggested when cells were incubated in the presence of nocodazole. The possible role of protein 2C in FMDV infection is discussed. The formation of 2C novel structures however had no effect on the trafficking of VSVG from the ER to the plasma membrane. Neither did the expression of 2B (which formed similar juxtanuclear structures to 2C), 3A or 3AB. The presence however of 2BC, the precursor of 2B and 2C in infected cells, had the effect of blocking VSVG in the ER by an unknown mechanism. FMDV hasbeen shown previously to down regulate the surface expression of MHC class I on the surface of infected cells (Sanz-Parra et al., 1998), and the results of this study implicate protein 2BC in the inhibitory effects of FMDV infection

No description available.

Foot-and-mouth disease viruses (FMDVs) constitute the aphthovirus genus of the Picornaviridae. The structures of Oi subtype viruses OiK and G67 have been solved and comparisons reveal the structural basis of monoclonal antibody escape mutations in G67. Escape mutations are seen to occur at surface-exposed residues and to provoke structural changes limited to the altered side chains. Comparisons of the structures of O₁ and O₁BFS (Acharya et al., Nature 337, 709-716 (1989)) suggest that changes occurring 'in-the-field' in response to polyclonal antibody pressure may be subtly different from mutations produced by monoclonal antibody pressure in vitro. Field mutations are seen to alter less exposed residues and to have more far-reaching structural effects than the in vitro, monoclonal provoked mutations. Crystals of G67 are seen to be 'intimately twinned', the data possessing extra symmetry due to a mis-packing of the crystals. A protocol, based on current real-space averaging procedures with a novel constraint imposed, has been used successfully to deconvolute these data. This method might be more generally applied to deconvolute the wavelength overlaps that occur when using the Laue method. The structures of C-S8cl and mutant SD6-6 have been solved at a resolution of 3.5Å. These structures enable comparisons between members of different FMDV serotypes to be made for the first time, namely: serotype 0 (O₁BFS) and serotype C (C-S8cl). Flexibility of the Arg-Gly-Asp containing G-H loop of VP1 is seen to be amongst the most conserved structural features. This loop is implicated in receptor binding and possible roles for the observed flexibility are discussed. The CS8cl structure also reveals more detail in previously disordered regions of the capsid, namely: the N-terminal residues of VP2 and potential myristate density under the 5-fold axis of the virion. Analysis of structures from the Protein Data Bank reveals different patterns of amino acid use in proteins involved in the two halves of the immune recognition event i.e. immunoglobulins and viruses. These patterns seem to be based not only on the characteristics of the most used amino acids but also on characteristics of the nucleotide codons used to code for them.

Thesis (PhD (Veterinary Tropical Diseases))--University of Pretoria, 2004. / Includes bibliographical references. Also available in print format.

Thesis (Ph.D.)(Bioinformatics))--University of Pretoria, 2008. / Includes summary.

Thesis (M. Phil.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 134-158).

Thesis (M.Sc.)(Microbiology)--University of Pretoria, 2006. / Includes summary. Includes bibliographical references. Available in print and online.

Thesis (Ph.D.) - University of St Andrews, August 2008.