In silico Evolutionary Divergence Analysis Suggests the Potentiality of Capsid Protein VP2 in Serotype-Independent Foot-and-Mouth Disease Virus Detection.

Salma Akter,Munawar Sultana,Israt Dilruba Mishu,A S M Rubayet Ul Alam,M Anwar Hossain

doi:10.3389/fvets.2020.00592

Abstract

Foot-and-mouth disease (FMD) is an economically devastating disease of the livestock worldwide and caused by the FMD virus (FMDV), which has seven immunologically distinct serotypes (O, A, Asia1, C, and SAT1–SAT3). Studies suggest that VP2 is relatively conserved among three surface-exposed capsid proteins (VP1–VP3) of FMDV, but the level of conservation has not yet been reported. Here we analyzed the comparative evolutionary divergence of VP2 and VP1 to determine the level of conservation in VP2 at different hierarchical levels of three FMDV serotypes (O, A, and Asia1) currently circulating in Asia through an in-depth computational analysis of 14 compiled datasets and designed a consensus VP2 protein that can be used for the development of a serotype-independent FMDV detection tool. The phylogenetic analysis clearly represented a significant level of conservation in VP2 over VP1 at each subgroup level. The protein variability analysis and mutational study showed the presence of 67.4% invariant amino acids in VP2, with the N-terminal end being highly conserved. Nine inter-serotypically conserved fragments located on VP2 have been identified, among which four sites showed promising antigenicity value and surface exposure. The designed 130 amino acid long consensus VP2 protein possessed six surface-exposed B cell epitopes, which suggests the possible potentiality of the protein for the development of a serotype-independent FMDV detection tool in Asia. Conclusively, this is the first study to report the comparative evolutionary divergence between VP2 and VP1, along with proposing the possible potentiality of a designed protein candidate in serotype-independent FMDV detection.

Highlights

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, causing a large-scale economic loss for livestock industries worldwide due to the rapid loss of productivity [1,2,3]
The current study aims at analyzing the comparative evolutionary divergence of VP2 and VP1, along with identification of the surface-exposed conserved antigenic sites in VP2 and designing a consensus VP2 protein as a potential candidate to develop a rapid and cost-effective tool for FMD diagnosis in the Asian region, which would be entirely serotype independent
The previous studies relate to our study regarding VP2 conservancy, we extended our analysis by determining the VP2-based cutoff divergence value at each subgroup level of three dominantly circulating Asian serotypes of FMD virus (FMDV) by Unweighted pair group method with arithmetic mean (UPGMA) phylogenetic analysis using 13 individual datasets, while the previous others showed only the serotype-dependent distinction of clusters by neighbor-joining phylogeny using a rather small dataset

Summary

Introduction

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, causing a large-scale economic loss for livestock industries worldwide due to the rapid loss of productivity [1,2,3]. The onset of FMD can cause extensive morbidity and mortality, resulting in a disastrous reduction in the yield of animal products. Extensive mutational variations result in the differentiation of the virus into seven immunologically distinct serotypes; O, A, C, Asia, and Southern African territories (SAT) 1–3 [7]. There are multiple topotypes that are usually related to the geographical region of disease occurrence or subtype and being identified based on a threshold of 15% nucleotide sequence divergence in the VP1 coding region. The high genetic diversity of the virus results in the emergence of many distinct lineages within a topotype, which show at least 7.5% VP1 nucleotide divergence [8, 9]. Further diversification divides the individual lineages into multiple sub-lineages, there is no established threshold for VP1 divergence among these sub-lineages

Methods

Results

Discussion

Conclusion