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Genome Sequences of Foot-and-Mouth Disease Virus SAT1 and SAT2 Strains from Kenya in 2014 to 2016.

ABSTRACT: Here, we report the near-complete genomes of three Southern African Territories 1 (SAT1) serotype strains and one SAT2 serotype strain of foot-and-mouth disease virus (FMDV) recently isolated from Kenya. Viral isolates were obtained from bovine epithelial tissues collected in 2014 and 2016 following outbreaks of foot-and-mouth disease (FMD). These near-complete genome sequences provide a critical update of Kenyan FMDV molecular epidemiology.

SUBMITTER: Palinski RM

PROVIDER: S-EPMC6728644 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Genome Sequences of Foot-and-Mouth Disease Virus SAT1 and SAT2 Strains from Kenya in 2014 to 2016.

Palinski Rachel M RM Sangula Abraham A Gakuya Francis F Bertram Miranda R MR Pauszek Steven J SJ Hartwig Ethan J EJ Smoliga George R GR Obanda Vincent V Omondi George G VanderWaal Kimberly K Arzt Jonathan J

Microbiology resource announcements 20190905 36

Here, we report the near-complete genomes of three Southern African Territories 1 (SAT1) serotype strains and one SAT2 serotype strain of foot-and-mouth disease virus (FMDV) recently isolated from Kenya. Viral isolates were obtained from bovine epithelial tissues collected in 2014 and 2016 following outbreaks of foot-and-mouth disease (FMD). These near-complete genome sequences provide a critical update of Kenyan FMDV molecular epidemiology. ...[more]

PMID: 31488534

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Project description:Foot-and-mouth disease virus (FMDV), particularly strains of the O and SAT serotypes, is notoriously unstable. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of immunity with a poor duration and hence require more frequent vaccinations to ensure protection. In silico calculations predicted residue substitutions that would increase interactions at the interpentamer interface, supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses in regard to their growth kinetics, antigenicity, plaque morphology, genetic stability, and temperature, ionic, and pH stability by using Thermofluor and inactivation assays in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutant for temperature and pH stability was the S2093Y single mutant, while other promising mutants were the E3198A, L2094V, and S2093H single mutants and the F2062Y-H2087M-H3143V triple mutant. Although the S2093Y mutant had the greatest stability, it exhibited smaller plaques, a reduced growth rate, a change in monoclonal antibody footprint, and poor genetic stability properties compared to those of the wild-type virus. However, these factors affecting production can be overcome. The addition of 1 M NaCl was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilizing SAT2 vaccines.IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of some serotypes, such as SAT2, affects the quality of vaccines and therefore the duration of immunity. We have shown that we can improve the stability of SAT2 viruses by mutating residues at the capsid interface through predictive modeling. This is an important finding for the potential use of such mutants in improving the stability of SAT2 vaccines in countries where FMD is endemic, which rely heavily on the maintenance of the cold chain, with potential improvement to the duration of immune responses.

Project description:Background and aimFoot-and-mouth disease virus (FMDV) serotypes A, O and South African Territories (SAT2) are endemic in Egypt; each is presented by a number of partially related topotypes and lineages, depending on their geographical origin. Continuous mutations and the emergence of new topotypes that lead to occasional vaccination failures were frequently recorded, so this study aimed to genetically characterize the circulating FMD virus strains in Egypt during 2013 and 2014 outbreaks, focusing on amino acids variations in VP1 region.Materials and methodsA total of 51 oral tissue samples were collected from cattle and buffaloes in 13 farms, and 38 individual cases showed clinical signs suspected to be FMD in six Egyptian Governorates (Cairo, Giza, Qaliubia, Fayoum, Sharquia, and Assiut). FMDV in collected samples was characterized by reverse transcription-polymerase chain reaction (RT-PCR) amplification of full VP1 region, sequencing, and phylogenetic analysis.ResultsOut of 51 samples, 44 (86.27%) were positive by RT-PCR using universal primers. Serotype O was predominant and detected in 31 samples (70.45%), serotype A was detected in 9 samples (20.45%), and then serotype SAT2 was identified in 4 samples (9.10%). Sequencing and phylogenetic analysis of VP1 demonstrated clustering of serotype O, A, and SAT2 in EA-3 topotype, ASIA topotype, and topotype VII, respectively. Serotype O is closely related to O/SUD/8/2008 with 94.6% identity but showed 14.6% differences from vaccine strain (O/PanAsia-2) of ME-SA topotype. Furthermore, Serotype A and SAT2 were closely related to recent circulating Egyptian isolates and vaccine strains type A/EGY/1/2012 (Asia topotype, lineage Iran-05) with identity 96.4% and vaccine strain of SAT2/EGY/A/2012 (topotype VII, lineage SAT2/VII/ALX-12) with identity 95.3%, respectively.ConclusionThe present study recommended further studies of serotype O to determine the immunogenic relationship between the vaccine strain and the new strains to attain maximum protection against circulating viruses.

Project description:Monoclonal-antibody (MAb)-resistant mutants were used to map antigenic sites on foot-and-mouth disease virus (FMDV), which resulted in the identification of neutralizing epitopes in the flexible ?G-?H loop in VP1. For FMDV SAT2 viruses, studies have shown that at least two antigenic sites exist. By use of an infectious SAT2 cDNA clone, 10 structurally exposed and highly variable loops were identified as putative antigenic sites on the VP1, VP2, and VP3 capsid proteins of SAT2/Zimbabwe (ZIM)/7/83 (topotype II) and replaced with the corresponding regions of SAT2/Kruger National Park (KNP)/19/89 (topotype I). Virus neutralization assays using convalescent-phase antisera raised against the parental virus, SAT2/ZIM/7/83, indicated that the mutant virus containing the TQQS-to-ETPV mutation in the N-terminal part of the ?G-?H loop of VP1 showed not only a significant increase in the neutralization titer but also an increase in the index of avidity to the convalescent-phase antisera. Furthermore, antigenic profiling of the epitope-replaced and parental viruses with nonneutralizing SAT2-specific MAbs led to the identification of two nonneutralizing antigenic regions. Both regions were mapped to incorporate residues 71 to 72 of VP2 as the major contact point. The binding footprint of one of the antigenic regions encompasses residues 71 to 72 and 133 to 134 of VP2 and residues 48 to 50 of VP1, and the second antigenic region encompasses residues 71 to 72 and 133 to 134 of VP2 and residues 84 to 86 and 109 to 11 of VP1. This is the first time that antigenic regions encompassing residues 71 to 72 of VP2 have been identified on the capsid of a SAT2 FMDV.Monoclonal-antibody-resistant mutants have traditionally been used to map antigenic sites on foot-and-mouth disease virus (FMDV). However, for SAT2-type viruses, which are responsible for most of the FMD outbreaks in Africa and are the most varied of all seven serotypes, only two antigenic sites have been identified. We have followed a unique approach using an infectious SAT2 cDNA genome-length clone. Ten structurally surface-exposed, highly varied loops were identified as putative antigenic sites on the VP1, VP2, and VP3 capsid proteins of the SAT2/ZIM/7/83 virus. These regions were replaced with the corresponding regions of an antigenically disparate virus, SAT2/KNP/19/89. Antigenic profiling of the epitope-replaced and parental viruses with SAT2-specific MAbs led to the identification of two unique antibody-binding footprints on the SAT2 capsid. In this report, evidence for the structural engineering of antigenic sites of a SAT2 capsid to broaden cross-reactivity with antisera is provided.

Dataset Information

Genome Sequences of Foot-and-Mouth Disease Virus SAT1 and SAT2 Strains from Kenya in 2014 to 2016.

Publications

Genome Sequences of Foot-and-Mouth Disease Virus SAT1 and SAT2 Strains from Kenya in 2014 to 2016.

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