Project Directorate on Foot-and-Mouth Disease, Mukteswar-Kumaon, Nainital 263138, Uttarakhand, India.
Virus Res. 2013 Sep;176(1-2):273-9. doi: 10.1016/j.virusres.2013.07.003. Epub 2013 Jul 12.
Foot-and-mouth disease virus (FMDV) is constantly evolving under neutralizing antibody pressure in either naturally infected or vaccinated animals. This study was carried out to understand the dynamics of evolution of antigenic sites. Neutralizing antibody-resistant populations of three strains of FMDV serotype O (INDR2/1975, IND120/2002 and IND271/2001) were isolated by serial propagation in BHK-21 cells in the presence of sub-neutralizing level of bovine vaccinal sera (BVS). In the partial neutralization escape variants, fixation of aa substitutions were observed at critical residues of all established antigenic sites of serotype O {144 of VP1 (site 1), 45 and 48 of VP1 (site 3), 72 and 134 of VP2 (Site 2)} except site 4 and 5. In majority of the variant populations, site 3 was found to be substituted and therefore immunodominance may not be associated with a particular site, rather it appears to be a virus strain and infected host specific affair. Substitutions were also observed in proximity to the identified residues {41 and 51 (βB-βC loop), 133, 140 and 143 (βG-βH loop), 201, 204 and 209 (C terminus) of VP1, 71 and 75 (βB-βC loop), 131 (βE-αB region), 174 and 179 (βG-βH loop) and 219 (C terminus) of VP3} within antigenic sites of serotype O or other serotypes which could be significant in terms of neutralizing antibody binding and immune escape. Presence of similar residues in the Indian field viruses as selected in the variants supports the importance of these sites in antigenic diversification of serotype O FMD virus.
口蹄疫病毒（FMDV）在自然感染或接种疫苗的动物中，不断受到中和抗体的压力而发生进化。本研究旨在了解抗原表位进化的动态。通过在存在亚中和水平牛疫苗血清（BVS）的情况下，在 BHK-21 细胞中连续传代，分离了三种血清型 O（INDR2/1975、IND120/2002 和 IND271/2001）的 FMDV 的中和抗体抗性群体。在部分中和逃逸变异体中，在所有已建立的 O 型血清型抗原表位的关键残基处观察到 aa 取代的固定，包括 VP1 的 144（位点 1）、VP1 的 45 和 48（位点 3）、VP2 的 72 和 134（位点 2），除了位点 4 和 5。在大多数变异群体中，发现位点 3被取代，因此免疫显性可能与特定的位点无关，而似乎是病毒株和感染宿主特有的。在 O 型或其他血清型的抗原表位内，也观察到了接近已确定的残基的取代，包括 VP1 的 41 和 51（βB-βC 环）、133、140 和 143（βG-βH 环）、201、204 和 209（C 末端）、VP3 的 71 和 75（βB-βC 环）、131（βE-αB 区）、174 和 179（βG-βH 环）和 219（C 末端），这可能在中和抗体结合和免疫逃逸方面具有重要意义。在变体中选择的印度田间病毒中存在类似的残基，支持这些位点在 O 型 FMD 病毒抗原多样化中的重要性。
