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The phylogenetic analysis of VP1 genomic region in foot-and-mouth disease virus serotype O isolates in Sri Lanka reveals the existence of 'Srl-97', a newly named endemic lineage.

ABSTRACT: Foot and mouth disease (FMD) has devastated the cattle industry in Sri Lanka many times in the past. Despite its seriousness, limited attempts have been made to understand the disease to ameliorate its effects-current recommendation for vaccines being based solely on immunological assessments rather than on molecular identification. The general belief is that the cattle population in Sri Lanka acquired the FMD virus (FMDV) strains via introductions from India. However, there could be endemic FMDV lineages circulating in Sri Lanka. To infer the phylogenetic relationships of the FMDV strains in the island, we sequenced the VP1 genomic region of the virus isolates collected during the 2014 outbreak together with a few reported cases in 2012 and 1997 and compared them to VP1 sequences from South Asia. The FMDV strains collected in the 2014 outbreak belonged to the lineage, Ind-2001d, of the topotype, ME-SA. The strains collected in 2012 and 1997 belonged to another lineage called 'unnamed' by the World Reference Laboratory for Foot and Mouth Disease (WRLFMD). Based on the present analysis, we designate the lineage 'unnamed' as Srl-97 which we found endemic to Sri Lanka. The evolutionary rates of Srl-97 and Ind-2001d in Sri Lanka were estimated to be 0.0004 and 0.0046 substitutions/site/year, respectively, suggesting that Srl-97 evolves slowly.

SUBMITTER: Abeyratne SAE

PROVIDER: S-EPMC5865751 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals that causes a significant economic burden globally. Vaccination is the most effective FMD control strategy. However, FMD virus (FMDV) particles are prone to dissociate when appropriate physical or chemical conditions are unavailable, such as an incomplete cold chain. Such degraded vaccines result in compromised herd vaccination. Therefore, thermostable FMD particles are needed for use in vaccines. This study generated thermostable FMDV mutants (M3 and M10) by serial passages at high temperature, subsequent amplification, and purification. Both mutants contained an alanine-to-threonine mutation at position 13 in VP1 (A1013T), although M3 contained 3 additional mutations. The selected mutants showed improved stability and immunogenicity in neutralizing antibody titers, compared with the wild-type (wt) virus. The sequencing analysis and cryo-electron microscopy showed that the mutation of alanine to threonine at the 13th amino acid in the VP1 protein (A1013T) is critical for the capsid stability of FMDV. Virus-like particles containing A1013T (VLPA1013T) also showed significantly improved stability to heat treatment. This study demonstrated that Thr at the 13th amino acid of VP1 could stabilize the capsid of FMDV. Our findings will facilitate the development of a stable vaccine against FMDV serotype O. IMPORTANCE Foot-and-mouth disease (FMD) serotype O is one of the global epidemic serotypes and causes significant economic loss. Vaccination plays a key role in the prevention and control of FMD. However, the success of vaccination mainly depends on the quality of the vaccine. Here, the thermostable FMD virus (FMDV) mutants (M3 and M10) were selected through thermal screening at high temperatures with improved stability and immunogenicity compared with the wild-type virus. The results of multisequence alignment and cryo-electron microscopy (cryo-EM) analysis showed that the Thr substitution at the 13th amino acid in the VP1 protein is critical for the capsid stability of FMDV. For thermolabile type O FMDV, this major discovery will aid the development of its thermostable vaccine.

Project description:Foot-and-mouth disease (FMD) affects the livestock industry in a transboundary manner. It is essential to understand the FMD phylodynamics to assist in the disease-eradication. FMD critically affects the Sri Lankan cattle industry causing substantial economic losses. Even though many studies have covered the serotyping and genotyping of FMD virus (FMDV) in Sri Lanka, there is a significant knowledge gap exists in understanding the FMDV phylodynamics in the country. In the present study, the VP1 genomic region of FMD viral isolates belonging to serotype C from Sri Lanka and other South Asian countries were sequenced. All the published VPI sequences of serotype C and most of the published VP1 sequences for lineage ME-SA/Ind-2001d of serotype O from Sri Lanka, India, and other South Asian countries were retrieved. The datasets of serotype C and serotype O were separately analyzed using Bayesian, maximum likelihood, and phylogenetic networking methods to infer the transboundary movements and evolutionary aspects of the FMDV incursions in Sri Lanka. A model-based approach was used to detect any possible recombination events of FMDV incursions. Our results revealed that the invasions of the topotype ASIA of serotype C and the lineage ME-SA/Ind-2001d have a similar pattern of transboundary movement and evolution. The haplotype networks and phylogenies developed in the present study confirmed that FMDV incursions in Sri Lanka mainly originate from the Indian subcontinent, remain quiet after migration, and then cause outbreaks in a subsequent year. Since there are no recombination events detected among the different viral strains across serotypes and topotypes, we can assume that the incursions tend to show the independent evolution compared to the ancestral viral populations. Thus, we highlight the need for thorough surveillance of cattle/ruminants and associated product-movement into Sri Lanka from other regions to prevent the transboundary movement of FMDV.

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The phylogenetic analysis of VP1 genomic region in foot-and-mouth disease virus serotype O isolates in Sri Lanka reveals the existence of 'Srl-97', a newly named endemic lineage.

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