Abstract
Improvements to sequencing protocols and the development of computational phylogenetics have opened up opportunities to study the rapid evolution of RNA viruses in real time. In practical terms, these results can be combined with field data in order to reconstruct spatiotemporal scenarios that describe the origin and transmission pathways of viruses during an epidemic. In the case of notifiable diseases, such as foot-and-mouth disease (FMD), these analyses provide important insights into the epidemiology of field outbreaks that can support disease control programmes. This study reconstructs the origin and transmission history of the FMD outbreaks which occurred during 2011 in Burgas Province, Bulgaria, a country that had been previously FMD-free-without-vaccination since 1996. Nineteen full genome sequences (FGS) of FMD virus (FMDV) were generated and analysed, including eight representative viruses from all of the virus-positive outbreaks of the disease in the country and 11 closely-related contemporary viruses from countries in the region where FMD is endemic (Turkey and Israel). All Bulgarian sequences shared a single putative common ancestor which was closely related to the index case identified in wild boar. The closest relative from outside of Bulgaria was a FMDV collected during 2010 in Bursa (Anatolia, Turkey). Within Bulgaria, two discrete genetic clusters were detected that corresponded to two episodes of outbreaks that occurred during January and March-April 2011. The number of nucleotide substitutions that were present between, and within, these separate clusters provided evidence that undetected FMDV infection had occurred. These conclusions are supported by laboratory data that subsequently identified three additional FMDV-infected livestock premises by serosurveillance, as well as a number of antibody positive wild boar on both sides of the border with Turkish Thrace. This study highlights how FGS analysis can be used as an effective on-the-spot tool to support and help direct epidemiological investigations of field outbreaks.
Highlights
Foot-and-mouth disease (FMD) is one of the most economically important animal diseases and notification of changes in disease status to the World Organisation for Animal Health (OIE) is compulsory
Several factors contribute to the high evolutionary rate of FMD virus (FMDV) including the high error-rate of the PLOS ONE | www.plosone.org viral RNA polymerase in combination with the fast rate of virus replication and large population size generated in infected cells [5]
These characteristics lead to the rapid fixation of mutations throughout the genome which are inherited by progeny viruses, a feature previously exploited to reconstruct transmission pathways of FMDV during field outbreaks of disease in the United Kingdom (UK) during 2001 [6,7,8] and 2007 [9]
Summary
Foot-and-mouth disease (FMD) is one of the most economically important animal diseases and notification of changes in disease status to the World Organisation for Animal Health (OIE) is compulsory. Several factors contribute to the high evolutionary rate of FMDV including the high error-rate of the PLOS ONE | www.plosone.org viral RNA polymerase (a characteristic shared with other RNA viruses) in combination with the fast rate of virus replication and large population size generated in infected cells [5]. These characteristics lead to the rapid fixation of mutations throughout the genome which are inherited by progeny viruses, a feature previously exploited to reconstruct transmission pathways of FMDV during field outbreaks of disease in the UK during 2001 [6,7,8] and 2007 [9]. Genetic variability of FMDV, often classified on the basis of the sequences coding for the VP1 capsid protein of the virus (624–657 nt length), is reflected by the presence of seven antigenically distinct serotypes [O, A, C, Asia 1 and Southern African Territories (SAT) 1, SAT 2 and SAT 3] plus a large number of temporally and spatially distributed subgroups (topotypes, strains, lineages and sub-lineages) [2]
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