Appendix 43

“New tools and challenges for progressive control”Open Session of the EuFMD Research Group, Vienna (Austria) 29 September ‐ 1 October 2010

Foot-and-Mouth Disease Virus Genotype Definitions and NomenclatureNick J. Knowles, Jemma Wadsworth, Jef M. Hammond and Donald P. King

Institute for Animal Health, Pirbright Laboratory,Ash Road, Pirbright, Woking, Surrey, GU24 0NF, UK.

1

Introduction• Foot-and-mouth disease viruses (FMDV) belonging to each of the

serotypes have been classified into a number of topotypes (VP1 genotypes which occupy distinct geographical niches).

• Currently, these number 11 for type O, 3 for type A, 3 for type C, 1 for type Asia 1, 9 for type SAT 1, 14 for type SAT 2 and 5 for type SAT 3.

• There are also a number of older viruses which are distinct or difficult to place within this framework.

• Within topotypes viruses are sometimes placed in named clusters, called genotypes, lineages or strains, which do not necessarily have consistent defining criteria.

2

Material & Methods• Phylogenetic trees were generated using the Neighbor-

joining (N-J) method with bootstrap re-sampling (MEGA 4.0).

• Bayesian evolutionary analysis was performed using the BEAST software package. The Bayesian Markov Chain Monte Carlo (MCMC) method, using virus isolation times, was used to generate dated trees.

• VP1 sequences of the prototype viruses were used in the construction of both trees.

3

Results• In general the tree topology was similar using the two

methodologies, however, the Bayesian trees were more informative concerning the evolution and dating of the viruses.

4

FMDV O•EURO-SA (Europe-South America)•ISA-1 (Indonesia 1)•ISA-2 (Indonesia 2)

•ME-SA (Middle East-South Asia)•SEA (Southeast Asia)•EA-1 (East Africa 1)•EA-2 (East Africa 2)•EA-3 (East Africa 3)•EA-4 (East Africa 4)•WA (West Africa)

•CATHAY (Far East)

•AFRICA?

•AFRICA•G-I•G-II•G-III•G-IV•G-V•G-VI•G-VII

•ASIA•EURO-SA

•AFRICA•ASIA•EURO-SA

5

FMDV A FMDV C

FMDV Asia 1•ASIA

O/CAM/3/98

A24/Cruzeiro/BRA/55

O/SUD/2/86

A/TAI/118/87

Asia1/IND/63/72

O1/Manisa/TUR/69

As1/IND/14/95

O/ETH/3/2004

O/IND/53/79

A/NGR/2/73

O/CIV/8/99

A/SUD/3/77

A/EGY/1/72

A15/Bangkok/TAI/60

O/Corrientes/ARG/06

C/GER/c26

A/IRN/1/96

O2/Brescia/ITL/47

C1/Santa_Pau/SPA/70

O/ETH/58/2005

O/UGA/3/2002

O/ISA/9/74

C/N65/Tadjikistan/USSR/67

O/Yunlin/TAW/97

As1/IRN/10/2004

O/HKN/6/83

O/ETH/2/2006

O/UKG/35/2001

O/SUD/62/63

As1/IND/762/2003

O/K83/79

A/IRN/1/2005

O/ISA/1/74O/JAV/5/72

C/PHI/7/84

As1/PAK/1/54

C3/Resende/BRA/55

As1/HKN/19/74

O3/VEN/51

A23/Kitale/KEN/64

O/K40/84

O/TAN/2/2004

C/UKG/149/34

C3/Indaial/BRA/71(78)

O1/BFS_1860/UK/67

O/ETH/1/2007

O/IRN/8/2005

A/IRN/2/87

C/IND/51/79

A/GHA/16/73

O/MYA/7/98

A/UGA/13/66

O/PHI/7/96

O/HKN/21/70

O/IND/R2/75

A11/GER/29

O/ISA/8/83

O/KEN/5/2002

A21/Lumbwa/KEN/64

O/UGA/17/98

As1/YNBS/CHA/58

A/KEN/42/66

A/IRN/22/99

As1/AFG/1/2001

C/KEN/32/70

As1/Shamir/ISR/89

O/GHA/5/93

O/ISA/1/62

A/Alem/ARG/81A12/UK/119/32

O/MAL/1/98

C/ETH/1/71

As1/IND/18/80

O/TAI/189/87

O/UGA/5/96

A22/IRQ/64

74.9669

56.1172

75.1104

38.5151

45.8859

90.3356

43.1733

75.7157

79.31

118.6734

54.9277

90.2554114.5486

136.4071

51.2784

66.9976

70.8175

79.5978

66.1745

87.9046

100.1505

35.9039

47.1699

37.1958

359.0329

26.7117

28.8446

71.1323

67.601

106.3017

30.4719

62.6362

105.9441

56.2367

98.4513

26.3657

89.2675

76.5078

36.5147

128.2172

55.3432

107.4232

257.7132

95.1057

70.1486

51.3784

31.3679

78.3674

89.3394

70.8911

127.4734

85.5037

100.2248

24.9942

79.0683

42.3732

79.9635

73.5995

306.9279

76.3459

48.9

106.4941

135.6281

60.8478

105.0769

85.8809

114.9956

91.7334

119.1207

123.4639

414.2077

146.3516

61.7553

78.5225

116.8245

120 years ago

6

Asia 1

O

A

C

ASIA

EURO-SA

EA-1

EA-2

AFRICA

ASIAEURO-SA

AFRICA

EA-3EA-4

ME-SA

SEA

CATHAY

ISA-1ISA-2

EURO-SA

WA

ASIA

Model: GTR+I+γConstant populationChain: 20,000,000Burn-in: 10%

Maximum cladecredibility tree

Appendix 43

“New tools and challenges for progressive control”Open Session of the EuFMD Research Group, Vienna (Austria) 29 September ‐ 1 October 2010

7

FMDV C Topotypes1926-2004

EURO-SA

AFRICA

ASIA

C1/Cadelbosco di Sopra/89C1/Villa Sesso/89

C1/S.Palo dEute/89C1/Villa Colli/89

C1/Brescia/64C1/Brescia/ITL/64

C1/Modena/89C1/Poutecchio Bibhieur/Italy/89

C1/Oberbayern/FRG/60 (X00130)C1/Perugia/ITL/63

C1/Santa Pau/SPA/70 (AJ133357)C1/Santa Pau/70

C/HUN/1/72C/USSR/2/90

C1/Noville/SWI/65C1/Noville/SWI/65 (AY593804)

C1/Detmold/FRG/60C/Cotes du Nord/FRA/74C1/Oberbayern/FRG/60 (AY593805)C/POR/2/80

C/Pyrenees Atlantiques/FRA/80C1/Serra de Daro/SPA/81 (C-S15)

C1/Barcelona/SPA/82 (C-S30)C/BEL/1/72

C/AUR/4/73C1/Vosges/FRA/60 (EVD)C1/Turup/DEN/61C1/Vosges/FRA/60

C1/Bombay/IND/64 (IVRI)C1/Loupoigne/BEL/53 (1)C1/Loupoigne/BEL/53C/CZE/3/89C1/Loupoigne/BEL/53 (2)C/FRA/2/66

C1/Haute Loire/FRA/69C2/Pando/URU/44

C2/Pando/URU/44 (EVD)C4/TDF/ARG/66 (AY593808)

C4/TDF/ARG/66C2/997/UK/53C2/997/UK/53 (EVD)

C/Leticia/COL/67C/Leticia/COL/70

C/General Roca/Cordoba/ARG/02/93 (AJ3062C/General Villegas/BA/ARG/93 (AJ306217)

C3/Sao Jose dos Campos/BRA/72C3/Goias/88

C3/Chaco/PAR/74C3/Cordoba/ARG/85 (L29062)C3/ARG/85 (AJ007347)

C/General Lamadrid/ARG/93 (AJ306213)C3/ARG/85 (M19762)

C/Salto/BA/ARG/91 (AJ308703)C3/San Antonio de Giles/ARG/92 (AJ308704

C/ANG/3/73C3/Indaial/BRA/71(78) (M90376)

C3/Indaial/BRA/71 (J02184)C3/Alegrete/BRA/82

C3/Santa Fe/ARG/75C3/Indaial/BRA/71 (K01202)

C3/Indaial/BRA/71 (AY593806)C/PHI/7/84 VS

C/PHI/6/89C/PHI/3/88

C/PHI/11/89C/PHI/3/94

C/PHI/4/94C3/PAR/69

C5/ARG/69 (AY593809)C5/BEL/1/69

C5/ARG/69C3/ARG/84 (M19761)

C/PHI/7/76C/PHI/1/79

C/ISR/4/70C/LEB/3/69C3/Resende/BRA/55 (AY593807)C3/ARG/83 (EVD)

C3/ARG/83C3/Resende/BRA/55 (M19760)C3/Resende/55

CGC WRLC1/GER/c.26 (CGC) (Madrid)

C/UKG/149/34 (AY593810)

EURO-SA

C/KEN/1/2004 (K6/04)C/KEN/32/70 (K267/67)C/KEN/5/96 (K14/96)C/K221/83 (Kenya)

C/ETH/1/71C/ETH/6/2005

C/ETH/7/2005

AFRICAC/CEY/4/71

C/SRL/4/78C/SRL/1/84

C/IND/3/83C/KUW/2/82

C/IND/9/82C/IND/7/76

C/IND/14/80C/IND/12/82C/IND/51/79 (IND/42/77*)C/IND/1/82

C/SAU/1/84C/SAU/12/84

C/NEP/35/96C/IND/63/96* (1991 IVRI)C/IND/147/93* (IVRI)

C/IND/26/93* (IVRI)C/IND/146/93* (IVRI)

C/NEP/1/94C/NEP/10/93

C/IND/66/96* (1991 IVRI)C/NEP/124/90

C/IND/67/96* (1991 IVRI)C/IND/64/96* (1991 IVRI)

C/IND/65/96* (1991 IVRI)C/IND/8/93* (1992 IVRI)

C/BAN/1/92C/BAN/2/92

C/BHU/10/91C/IND/89/92* (1991 IVRI)

C/BHU/7/91C/IND/9/93* (1992 IVRI)

C/IND/7/92* (1991 IVRI)C/IND/136/92* (IVRI)

ASIA0.02

Topotype not known

NJ tree

0.0100.0200.0300.0400.0500.0

A24/Cruzeiro/BRA/55

SAT3/BEC/20/61

SAT2/KEN/3/57

SAT3/BEC/1/65

SAT3/SA/57/59

SAT2/RHO/1/48

SAT2/ETH/2/91

SAT2/ZAI/1/82

SAT1/T155/71

SAT1/UGA/1/97

SAT1/BEC/1/48

SAT2/NIG/2/75

SAT3/KNP/10/90

SAT2/GAM/8/79

SAT1/BOT/1/68

SAT3/ZIM/P25/91_(UR-7)

SAT1/UGA/13/74

SAT2/ZAI/1/74

SAT2/ZIM/14/2002

SAT1/UGA_BUFF/21/70

SAT2/BOT/P3/98_(B29)

SAT1/RHO/5/66

SAT3/ZAM/P2/96_(MUL-4)

SAT2/RWA/1/2000

SAT2/ETH/1/90

SAT3/UGA/2/97

SAT2/KEN/1/84

SAT2/SAU/6/2000

SAT1/NIG/11/75

SAT1/ETH/3/2007

SAT1/ISR/4/62

SAT2/KEN/2/84

SAT2/SA/106/59

SAT2/GHA/2/90

SAT2/UGA/19/98

SAT2/ZIM/7/83

SAT2/UGA/51/75

SAT3/UGA_BUFF/27/70

SAT2/CAR/8/2005

SAT2/ETH/2/2007

SAT1/ZIM/23/2003

SAT2/SUD/6/77

SAT2/ZIM/5/81

SAT1/SUD/3/76

SAT1/RV/11/37

SAT2/ANG/4/74

137.6382

167.8403

210.5827

97.3099

92.4326

455.4043

87.1995

155.4316201.9919

141.6076

101.3106

260.7143

111.3776

79.9792

359.9438

189.4959

199.7192

101.4153

109.5911

88.4598

229.1244

96.0793

86.594

96.9347

179.8027

240.2197

212.559

173.5708

112.3445

176.1991

143.9747

90.5951

140.8263

76.8002

173.2776554.8243

146.1399

35.5257

143.8035

145.8174

62.7246

184.3056

115.6589

123.2546

120 years ago

SAT 3

SAT 2

SAT 1

8

Model: GTR+I+γConstant populationChain: 20,000,000Burn-in: 10%

Maximum cladecredibility tree

SAT 1 topotypes

I

II

III

IV

V

VI

VII

VIII

IX

NSA-1 (North Southern Africa 1)

ESA-1(East Southern Africa 1)

WSA-1(West Southern Africa 1)

EA-1(East Africa 1)

EA-2(East Africa 2)

EA3(East Africa 3)

EA-4(East Africa 4)

WA-1(West Africa 1)

NCA-1(North Central Africa 1)

9

SAT 2 topotypes

WA-2(West Africa 2)

NCA-1(North Central Africa 1)

CA-1(Central Africa 1)

EA-2(East Africa 2)

EA-3(East Africa 3)

EA4(East Africa 4)

EA-5(East Africa 5)

CA-2(Central Africa 2)

ESA-1(East Southern Africa 1)

WSA-1(West Southern Africa 1)

WSA-2(West Southern Africa 2)

EA-1(East Africa 1)

WA-1(West Africa 1)

WSA-3(West Southern Africa 3)

GUINEA

IIIIIIIVVVIVIIVIIIIXXXIXIIXIIIXIV

10

SAT 3 topotypesESA-1

(East Southern Africa 1)NSA-1

(North Southern Africa 1)

NSA-2(North Southern Africa 2)

EA-1 East Africa 1)

WSA-1 (West Southern Africa 1)

I

II

III

IV

V

11

Bayesian analyses• Within-topotype diversity only dates back less than 120 years

• This suggests that almost all type O, A and C viruses were introduced into Africa following the African Rinderpest Pandemic of the 1890’s.

▫ Type O: two introductions, probably from Asia, i) the ancestor of EA-1/EA-3/EA-4/WA and ii) the ancestor of EA-2.

▫ Type A: one introduction from Europe or Asia.

▫ Type C: one introduction from Europe or Asia (possibly in the 1940’s) and one from South America circa 1973.

12

Appendix 43

“New tools and challenges for progressive control”Open Session of the EuFMD Research Group, Vienna (Austria) 29 September ‐ 1 October 2010

Summary• The topotypes of FMDV O, A and C have been assigned

geographically-based names (e.g. O WEST AFRICA), while those belonging to the SAT types have been given arbitrary numbers (in Roman numeral format).

• We suggest that the former system is more informative and should be adopted for the SAT topotypes.

• Using both Bayesian and distance methods to construct trees provides a better basis for the definition of genetic groupings below the level of serotype.

13

Questions

• How should we define FMDV topotypes?

• How should we define FMDV strains or named lineages?

14

Acknowledgements

• Funding from Defra, UK

15