Reconstruction of the Transmission History of RNA Virus Outbreaks Using Full Genome Sequences: Foot-and-Mouth Disease Virus in Bulgaria in 2011

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.

Multiple introductions of serotype O foot-and-mouth disease viruses into East Asia in 2010–2011

“…The rate of nucleotide substitutions (per site per year) was 4.94 × 10 -3 (95% highest posterior density - HPD: 3.40 × 10 -3 - 6.58 × 10 -3 ) which are comparable to the rates observed during the FMDV outbreaks in UK during 2001 and 2007 [4,9,33] and Bulgaria in 2011 [11]. The most recent common ancestor (MRCA) was estimated to be in the 1990s (21 st February 1995; 95% HPD: 26 th October 1990 -16 th April 1999, dark blue bar, Figure 6).…”

Foot-and-mouth disease: past, present and future

“…VP1 sequence based phylogenetic analyses have been used widely to deduce evolutionary dynamics, epidemiological relationships among the genetic lineages and in the tracing of the origin and movement of outbreak strains [8-12]. …”

A thiazepino[4,5-a]benzimidazole derivative hampers the RNA replication of Eurasian serotypes of foot-and-mouth disease virus

“…To investigate the effect of continuous treatment with sub-optimal and increasing concentrations of CHI-83, the complete FMDV genome (except for the poly(C) region) of the resistant mutant virus, the virus control and the original virus was amplified, sequenced and analysed as described before [18,19].…”

“…Briefly, viral RNA was extracted and reverse-transcribed using SuperScript™ III Reverse Valdazo-Gonzalez et al [19].…”