Evolution and molecular epidemiology of foot and mouth disease virus in Bangladesh

Abstract

Foot and mouth disease (FMD) in cloven-hoofed animals is considered an economically devastating disease for livestock sector in Bangladesh and globally. The World Organization for Animal Health (OIE) and FAO proposed a strategy of 5-step FMD eradication process from the epidemic’s regions. Of which 0-2 steps are identification of epidemiology studies and identification appropriate causing FMDV circulating in the regions and selection of effective vaccine as it is the only appropriate step to control the FMD. On the background our laboratory has been working science 2011 and this thesis presents last 10 years (2012-2021) FMDV epidemiology and identification of a new genotype MYMBD21 under the lineage SA- 2018 most recently circulating in Bangladesh from 2021. This research including 32 districts and 71 outbreaks to reveal epidemiological patterns and evolutionary trends of FMDV over the past 10 years (2012-2021). Isolation of FMDV in cell culture BHK 21 cell line, VP1 gene and whole viral genome sequencing techniques combined with bioinformation tools are used for epidemiological studies and characterization of new novel genotype MYMBD21. The findings revealed that 54.7% prevalence of FMD with the majority of outbreaks occurring during the rainy season. Different risk factors such as age, gender, farming system and vaccination status demonstrated a significant association with FMD cases which was confirmed (p<0.05). Genotype O the most predominated over the variant A (11%) and variant Asia1 (4%). Emergence of Novel sublineages, Ind-2001BD1(Ind-2001e) and Ind-2001BD2 were reported under serotype O, the G-IX lineage of serotype Asia1 emerged in 2018, and most recently in 2021, a new genotype named MYMBD21 under the lineage SA-2018 was detected for the first time in Bangladesh. Until now, Ind-2001e (Ind-2001BD1) sublineage under serotype O became the predominant sublineage in Bangladesh. From the mutational trend analysis, highly variable sites were observed at positions 138 and 140 within the G-H loop for serotype O. For serotype A and Asia1, 45th and 44th remains in the B-C loop revealed the highest amino acid variations, respectively. A changing mutational pattern among the 2012-21 FMDV O, A and Asia 1 isolates were also observed. The whole genomes of ten FMDVs were sequenced from 2012 to 2021. In 2018, A new era O/ME-SA/2018 was detected in India which was also found to circulate in Bangladesh in 2021 with a significant Virus Protein 1 (VP1) nucleotide divergence (5-6%) suggesting the evolution of a novel sublineage, MYMBD21. This study reported the first complete genome sequence of the FMDV isolate, BAN/MY/My-466/2021 (shortly named My-466) of the MYMBD21 sublineage under the O/ME-SA/2018 lineage. The genome is 8,216 nucleotides long with 6,996 nucleotides open reading frame flanked by 5 UTR (1-1100) and 3 UTR (8097-8216). More stability has been identified in non-structural proteins as compared to proteins with structural characteristics. Mutation analysis against available field vaccine and proposed local vaccine strains revealed that VP1 was highly variable among the structural proteins with crucial mutations in the major antigenic region, G-H loop. These mutations were responsible for antigen-specific polymorphism regarding both current and proposed vaccine strains. And that was evidenced by the G-H loop displacement in a superimposed 3D model of VP1 of the isolate against vaccine strains. In conclusions, these findings of the studies are crucial to understand the FMD situation and designing necessary preventive steps according to the Progressive Control Pathway for FMD Control (PCP-FMD) in Bangladesh. The complete genome information of the circulating strains would be valuable for revealing the evolutionary pattern which is also necessary to formulate whole virus vaccines using appropriate strain to control the FMDs.