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Transmission pathways of foot-and-mouth disease virus in the United Kingdom in 2007.

Cottam EM, Wadsworth J, Shaw AE, Rowlands RJ, Goatley L, Maan S, Maan NS, Mertens PP, Ebert K, Li Y, Ryan ED, Juleff N, Ferris NP, Wilesmith JW, Haydon DT, King DP, Paton DJ, Knowles NJ - PLoS Pathog. (2008)

Bottom Line: Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs.Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols).Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August.

View Article: PubMed Central - PubMed

Affiliation: Institute for Animal Health, Pirbright Laboratory, Pirbright, Woking, Surrey, United Kingdom.

ABSTRACT
Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.

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Analysis of sequence data.A) Statistical parsimony analysis by TCS [19] of complete genome sequences of 14 FMDVs; connecting lines represent a nucleotide substitution, thicker lines represent non-synonymous substitutions, with substitutions indicative of adaptation to cell culture coloured green. Sequenced haplotypes (red circles), and putative ancestral virus haplotypes (white circles) are shown. AY593815 is a previously published sequence [21] of FMDV O1 BFS 1860. The asterisk indicates the start of the tree in 2B). B) Lesion age derived infection profiles of holdings overlaid with the outbreak virus geneology. The orange shading estimates the time when animals with lesions were present from the oldest lesion age at post-mortem [22]. For IP2c, there were no clinical signs of disease. The light blue shading represents incubation periods for each holding, estimated to begin no more than 14 days prior to appearance of lesions [23]. The dark blue shading is the infection date based on the most likely incubation time for this strain of 2–5 days [24]. Each UK 2007 outbreak virus haplotype is plotted according to the time the sample was taken from the affected animal (x axis). The dashed lines link the TCS tree together but do not denote any genetic change.
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ppat-1000050-g002: Analysis of sequence data.A) Statistical parsimony analysis by TCS [19] of complete genome sequences of 14 FMDVs; connecting lines represent a nucleotide substitution, thicker lines represent non-synonymous substitutions, with substitutions indicative of adaptation to cell culture coloured green. Sequenced haplotypes (red circles), and putative ancestral virus haplotypes (white circles) are shown. AY593815 is a previously published sequence [21] of FMDV O1 BFS 1860. The asterisk indicates the start of the tree in 2B). B) Lesion age derived infection profiles of holdings overlaid with the outbreak virus geneology. The orange shading estimates the time when animals with lesions were present from the oldest lesion age at post-mortem [22]. For IP2c, there were no clinical signs of disease. The light blue shading represents incubation periods for each holding, estimated to begin no more than 14 days prior to appearance of lesions [23]. The dark blue shading is the infection date based on the most likely incubation time for this strain of 2–5 days [24]. Each UK 2007 outbreak virus haplotype is plotted according to the time the sample was taken from the affected animal (x axis). The dashed lines link the TCS tree together but do not denote any genetic change.

Mentions: The UK 2007 FMD outbreaks were characterised by the emergence of two temporally and spatially distinct clusters. The genetic relationships of FMDV present in eleven field samples from the 2007 outbreak, three cell culture derived laboratory viruses (see Table S1) used at the Pirbright site during July 2007 (designated IAH1, IAH2 and MAH) and a published sequence of O1 BFS 1860 (AY593815) are illustrated in Figure 2A. Whereas IAH1 and the virus from which the published sequence was derived are believed to have been passaged no more than ten times in cell cultures, the IAH2 and MAH viruses had been extensively adapted to grow in a baby hamster kidney cell line (Table S1). In natural hosts, FMDV attaches to integrin receptors on the cell surface [10]. However, when grown in cell cultures, the virus may adapt to attach to heparan sulphate (HS), through acquisition of positively charged amino acid residues on the virus coat at positions VP2134 and/or VP356 [11],[12]. An additional change from a negatively charged amino acid residue at VP360 to a neutral residue often occurs but may not be essential for HS binding [11]. IAH1 and the previously sequenced isolate of O1 BFS 1860 have lysine at VP2134, histidine at VP356 and aspartic acid at VP360, none of the residues associated with HS binding, whereas substitutions at VP356 (arginine) and VP360 (glycine) are present in MAH and IAH2, consistent with their history of extensive culture passage (Table 2). The presence of the HS binding-associated substitution at residue VP360 (aspartic acid to glycine) in all but one of the field viruses provides evidence that a cell culture adapted virus is an ancestor of the outbreak. Since this residue is not critical for HS binding it is less likely to undergo reversion [11],[12]. The wild type configurations at VP356 in all of the outbreak viruses and at VP360 in the IP5 virus most likely reflect reversions that have been selected upon replication within the animal host. It is known that there is a strong selection pressure for the reversion at VP356 when FMDV replicates in cattle [11].


Transmission pathways of foot-and-mouth disease virus in the United Kingdom in 2007.

Cottam EM, Wadsworth J, Shaw AE, Rowlands RJ, Goatley L, Maan S, Maan NS, Mertens PP, Ebert K, Li Y, Ryan ED, Juleff N, Ferris NP, Wilesmith JW, Haydon DT, King DP, Paton DJ, Knowles NJ - PLoS Pathog. (2008)

Analysis of sequence data.A) Statistical parsimony analysis by TCS [19] of complete genome sequences of 14 FMDVs; connecting lines represent a nucleotide substitution, thicker lines represent non-synonymous substitutions, with substitutions indicative of adaptation to cell culture coloured green. Sequenced haplotypes (red circles), and putative ancestral virus haplotypes (white circles) are shown. AY593815 is a previously published sequence [21] of FMDV O1 BFS 1860. The asterisk indicates the start of the tree in 2B). B) Lesion age derived infection profiles of holdings overlaid with the outbreak virus geneology. The orange shading estimates the time when animals with lesions were present from the oldest lesion age at post-mortem [22]. For IP2c, there were no clinical signs of disease. The light blue shading represents incubation periods for each holding, estimated to begin no more than 14 days prior to appearance of lesions [23]. The dark blue shading is the infection date based on the most likely incubation time for this strain of 2–5 days [24]. Each UK 2007 outbreak virus haplotype is plotted according to the time the sample was taken from the affected animal (x axis). The dashed lines link the TCS tree together but do not denote any genetic change.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2277462&req=5

ppat-1000050-g002: Analysis of sequence data.A) Statistical parsimony analysis by TCS [19] of complete genome sequences of 14 FMDVs; connecting lines represent a nucleotide substitution, thicker lines represent non-synonymous substitutions, with substitutions indicative of adaptation to cell culture coloured green. Sequenced haplotypes (red circles), and putative ancestral virus haplotypes (white circles) are shown. AY593815 is a previously published sequence [21] of FMDV O1 BFS 1860. The asterisk indicates the start of the tree in 2B). B) Lesion age derived infection profiles of holdings overlaid with the outbreak virus geneology. The orange shading estimates the time when animals with lesions were present from the oldest lesion age at post-mortem [22]. For IP2c, there were no clinical signs of disease. The light blue shading represents incubation periods for each holding, estimated to begin no more than 14 days prior to appearance of lesions [23]. The dark blue shading is the infection date based on the most likely incubation time for this strain of 2–5 days [24]. Each UK 2007 outbreak virus haplotype is plotted according to the time the sample was taken from the affected animal (x axis). The dashed lines link the TCS tree together but do not denote any genetic change.
Mentions: The UK 2007 FMD outbreaks were characterised by the emergence of two temporally and spatially distinct clusters. The genetic relationships of FMDV present in eleven field samples from the 2007 outbreak, three cell culture derived laboratory viruses (see Table S1) used at the Pirbright site during July 2007 (designated IAH1, IAH2 and MAH) and a published sequence of O1 BFS 1860 (AY593815) are illustrated in Figure 2A. Whereas IAH1 and the virus from which the published sequence was derived are believed to have been passaged no more than ten times in cell cultures, the IAH2 and MAH viruses had been extensively adapted to grow in a baby hamster kidney cell line (Table S1). In natural hosts, FMDV attaches to integrin receptors on the cell surface [10]. However, when grown in cell cultures, the virus may adapt to attach to heparan sulphate (HS), through acquisition of positively charged amino acid residues on the virus coat at positions VP2134 and/or VP356 [11],[12]. An additional change from a negatively charged amino acid residue at VP360 to a neutral residue often occurs but may not be essential for HS binding [11]. IAH1 and the previously sequenced isolate of O1 BFS 1860 have lysine at VP2134, histidine at VP356 and aspartic acid at VP360, none of the residues associated with HS binding, whereas substitutions at VP356 (arginine) and VP360 (glycine) are present in MAH and IAH2, consistent with their history of extensive culture passage (Table 2). The presence of the HS binding-associated substitution at residue VP360 (aspartic acid to glycine) in all but one of the field viruses provides evidence that a cell culture adapted virus is an ancestor of the outbreak. Since this residue is not critical for HS binding it is less likely to undergo reversion [11],[12]. The wild type configurations at VP356 in all of the outbreak viruses and at VP360 in the IP5 virus most likely reflect reversions that have been selected upon replication within the animal host. It is known that there is a strong selection pressure for the reversion at VP356 when FMDV replicates in cattle [11].

Bottom Line: Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs.Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols).Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August.

View Article: PubMed Central - PubMed

Affiliation: Institute for Animal Health, Pirbright Laboratory, Pirbright, Woking, Surrey, United Kingdom.

ABSTRACT
Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.

Show MeSH
Related in: MedlinePlus