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Foot-and-mouth disease virus (FMDV) serotype A exhibits a higher degree of genetic and antigenic diversity resulting in frequent vaccine failure due to serological mismatch between the vaccine and heterologous strains. Currently, knowledge on the molecular basis of antigenic relationships among the FMDVs is limited; nevertheless, intratype antigenic variation due to mutation(s) is widely considered as the main hurdle to appropriate FMD vaccine development. Here, we studied genetic and antigenic variations of four FMDV serotype A isolates, BAN/GA/Sa-197/2013 (BAN-197), BAN/CH/Sa-304/2016 (BAN-304), BAN/DH/Sa-307/2016 (BAN-307) and BAN/DH/Sa-310/2017 (BAN-310) circulating in Bangladesh during 2013-2017. Initially, antigenic relationships (r 1 -values) of the field isolates were evaluated by the two-dimensional microneutralization test (2D-MNT) using the hyperimmune antisera raised in cattle against the vaccine strain, BAN-304. Interesingly, the results showed protective serological cross-reactivity (r 1 -values > 0.4) between the vaccine strain and the field isolates, BAN-307 and BAN-310, except BAN-197 that substantially mismatched (r 1  = 0.129 ± 0.043) with the BAN-304. Although VP1-based phylogeny grouped all the isolates within the same sublineage C (a subgroup of VP3 Δ59 variant) under the lineage A/ASIA/G-VII, strikingly, computational analyses of the viral capsid proteins demonstrated significant deviation at the VP1 G-H loop of BAN-197 from the vaccine strain, while VP(2-4) of both isolates were structurally conserved. To bridge the gap of how the distortion of the G-H loop and consequent antigenic hetergeneity occurred in BAN-197, we performed in silico combinatorial substitutions of the VP1 mutant amino acids (aa) of BAN-197 with the respective residues in BAN-304. Remarkably, our analyses revealed that two substitutions of distantly located aa at B-C (T48I:threonine → isoleucine) and G-H (A143V:alanine → valine) loops, in combination, distorted the VP1 G-H loop. Overall, this work contributes to understanding the molecular basis of antigenic relationships operating in serotype A FMDVs and the selection of suitable vaccine strain(s) for effective prophylaxis of FMD based on VP1-based analyses., (© 2020 Blackwell Verlag GmbH.)

Foot-and-mouth disease (FMD) is endemic in Bangladesh, and the implementation of a control programme for this disease is at an early stage, according to the FAO- and OIE-proposed Progressive Control Pathway for FMD (PCP-FMD) Roadmap. To develop an effective control programme, understanding of foot-and-mouth disease virus (FMDV) serotypes, even subtypes within the serotypes is essential. The present investigation aims at viral VP1 coding region sequence-based analysis of FMD samples collected from 34 FMD outbreaks during 2012-2016 in Bangladesh. Foot-and-mouth disease virus (FMDV) serotype O was responsible for 82% of the outbreaks in Bangladesh, showing its dominance over serotype A and Asia1. The VP1 phylogeny revealed the emergence of two novel sublineages of serotype O, named as Ind2001BD1 and Ind2001BD2, within the Ind2001 lineage along with the circulation of Ind2001d sublineage in Bangladesh, which was further supported by the multidimensional scaling with distinct clusters for each sublineage. The novel sublineages had evident genetic variability with other established sublineages within Ind2001 lineage. Ten mutations with three or more amino acid variations were detected within B-C loop, G-H loop and C-terminal region of the VP1 protein of FMDV serotype O viruses isolated exclusively from Bangladesh. Furthermore, two amino acid substitutions at positions 197 and 198 within the VP1 C-terminal region are unique to the novel sublineages. The existence of widespread genetic variations among circulatory FMDV serotype O viruses makes the FMD control programme complex in Bangladesh. Adequate epidemiological data, disease reporting, animal movement control, appropriate vaccination and above all stringent policies of the government are necessary to combat FMD in Bangladesh., (© 2018 Blackwell Verlag GmbH.)

Foot-and-mouth disease virus (FMDV) serotypes O, A and Asia1 are responsible for significant number of disease outbreaks in Bangladesh; however serotype Asia1 has not been reported in circulation since 1996. The present investigation reports the detection of serotype FMDV Asia1 from local farms in 2012 and 2013 outbreaks. The farms were located in Jessore and Gazipur districts, and one of these farms was under vaccine control programme. Phylogenetic analysis of the complete VP1 gene revealed that FMDV Asia1 is under genetic lineage C having close similarity to the Asia1 sequences of Indian origin. The circulatory genotype Asia1 showed VP1 protein sequence heterogeneity of eight amino acid substitutions within the G-H loop with the vaccine strain [IND 63/72 (AY304994)] used in vaccination programme. ELISA assay revealed that, of seven, only one local field serum sample (cattle vaccinated 38 days earlier) was positive at a titre level of >2.4 (log10) but failed to protect the cattle from infection occurred by the virus. This investigation focused that the eight amino acid substitution in VP1 protein at G-H loop of the locally circulated FMDV serotype Asia1 strain may be a reason for current vaccination failure., (© 2014 The Society for Applied Microbiology.)