Susceptibility to foot and mouth disease virus infection in vaccinated cattle, and host BoLA A and BoLA DRB3 genes polymorphism

Abstract

The vaccination of the susceptible animal population against FMDV remains the most important measure to control the virus and prevent economic loss. Occurrence of infection in vaccinated animals is well-known in some diseases and is termed as breakthrough infection. The reasons include host genetic factors which can play an important role resulting in differences in susceptibility of animals to virus infection even with vaccine induced protective immune response. The Major Histocompatibility Complex (MHC) of bovines i.e. Bovine Leukocyte Antigen (BoLA) is important for antigen presentation. The BoLA DRB3 allele, which codes for the beta chain in Class II antigen, has been extensively studied and numerous reports have previously shown association of polymorphism in the gene with resistance/ susceptibility to several bacterial and viral diseases. In addition, previous studies have shown relationship between BoLA Class I and resistance or susceptibility to different diseases in cattle. The present study investigated the polymorphism in BoLA DRB3 and BoLA gene sequences of host and their relation with breakthrough FMDV infection in vaccinated animals. The study has identified three polymorphic sites each in both the genes which correlate with evidence of recent infection indicating their role in determining susceptibility of vaccinated animals to FMDV infection. Our limited study was performed on a relatively small samples size collected from one region of country. Further validation would require more detailed investigations on larger sample size.

Supplementary information: The online version contains supplementary material available at 10.1007/s13337-021-00754-8.

Keywords: BoLA A; BoLA DRB3; FMDV; Polymorphism.

Fig. 1

A fraction of vaccinated cattle serum samples which had protective antibody titers against FMDV Serotype O, A and Asia 1 above protection levels, also tested positive for antibodies against 3AB₃ non-structural proteins of FMD virus. Antibody titres (log₁₀) of protective antibody levels against FMD Serotype O, A and Asia 1 in animal serum samples were investigated using sd-LPBE test. Most of the samples tested positive for antibodies against all 3 serotypes with titres above protection level of 1.8 (Fig. 1a). The serum samples were then tested for presence of antibodies against 3AB₃ non-structural proteins of FMD virus using 3AB₃ DIVA ELISA. Eleven samples tested positive with titres above threshold (PP > 40) indicating evidence of recent infection (Fig. 1b)

Fig. 2

The BoLA DRB3 Exon 2 and BoLA A genes sequences of vaccinated cattle showed nucleotide polymorphism which showed correlation with their DIVA status. The nucleotide sequences of BoLA DRB3 Exon 2 gene of vaccinated and DIVA positive animals were compared with sequences in vaccinated and DIVA negative animals. The analysis showed nucleotide polymorphism at three sites which strongly correlated with DIVA status of animal (Fig. 2a). The nucleotide sequences of BoLA A gene also showed nucleotide polymorphism at three sites which also strongly correlated with DIVA status of animal (Fig. 2b)

Fig. 3

The predicted amino acid sequences of BoLA DRB3 Exon 2 and BoLA A proteins in vaccinated cattle showed amino acid polymorphism which correlated with their DIVA status. The sequence logo representation of the predicted amino acids sequence of BoLA DRB3 protein show polymorphism at position 27, 72 and 75 (Fig. 3a), and of predicted BoLA A amino acid sequence show polymorphism at position 44, 65 and 112 of BoLA A protein (Fig. 3b)

Fig. 4

The predicted protein structure models of BoLA DRB3 protein and BoLA A protein show location and structural relation between amino acids at sites of DIVA status associated polymorphism. The predicted structure of BoLA DRB3 protein showed that the amino acids involved in DIVA status associated polymorphism were structurally closely located and formed part of a close pocket on the protein surface (Fig. 4a). The predicted structure of BoLA A protein showed that the amino acids involved in DIVA associated polymorphism were distributed at different positions with no structural proximity (Fig. 4b)