Genetic Basis of Antigenic Variation of SAT3 Foot-And-Mouth Disease Viruses in Southern Africa

Lorens Maake; William T Harvey; Lia Rotherham; Pamela Opperman; Jacques Theron; Richard Reeve; Francois F Maree

doi:10.3389/fvets.2020.00568

Genetic Basis of Antigenic Variation of SAT3 Foot-And-Mouth Disease Viruses in Southern Africa

Front Vet Sci. 2020 Sep 8:7:568. doi: 10.3389/fvets.2020.00568. eCollection 2020.

Authors

Lorens Maake^{1

2}, William T Harvey³, Lia Rotherham¹, Pamela Opperman^{1

4}, Jacques Theron², Richard Reeve³, Francois F Maree^{1

2}

Affiliations

¹ Vaccine and Diagnostic Development Programme, Onderstepoort Veterinary Institute, Agricultural Research Council, Pretoria, South Africa.
² Department of Biochemistry, Genetics and Microbiology, Faculty of Agricultural and Natural Sciences, University of Pretoria, Pretoria, South Africa.
³ Boyd Orr Centre for Population and Ecosystem Health, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
⁴ Department of Animal Production Studies, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.

Abstract

Foot-and-mouth disease (FMD) continues to be a major burden for livestock owners in endemic countries and a continuous threat to FMD-free countries. The epidemiology and control of FMD in Africa is complicated by the presence of five clinically indistinguishable serotypes. Of these the Southern African Territories (SAT) type 3 has received limited attention, likely due to its restricted distribution and it being less frequently detected. We investigated the intratypic genetic variation of the complete P1 capsid-coding region of 22 SAT3 viruses and confirmed the geographical distribution of five of the six SAT3 topotypes. The antigenic cross-reactivity of 12 SAT3 viruses against reference antisera was assessed by performing virus neutralization assays and calculating the r₁-values, which is a ratio of the heterologous neutralizing titer to the homologous neutralizing titer. Interestingly, cross-reactivity between the SAT3 reference antisera and many SAT3 viruses was notably high (r₁-values >0.3). Moreover, some of the SAT3 viruses reacted more strongly to the reference sera compared to the homologous virus (r₁-values >1). An increase in the avidity of the reference antisera to the heterologous viruses could explain some of the higher neutralization titers observed. Subsequently, we used the antigenic variability data and corresponding genetic and structural data to predict naturally occurring amino acid positions that correlate with antigenic changes. We identified four unique residues within the VP1, VP2, and VP3 proteins, associated with a change in cross-reactivity, with two sites that change simultaneously. The analysis of antigenic variation in the context of sequence differences is critical for both surveillance-informed selection of effective vaccines and the rational design of vaccine antigens tailored for specific geographic localities, using reverse genetics.

Keywords: Southern African Territory (SAT) type 3; antigenic; antigenic matching; cross-reactivity; foot-and-mouth disease (FMD); phylogeny; virus neutralization test.

Abstract

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