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Morgan R. Herod, Sarah Gold, Lidia Lasecka-Dykes, Caroline Wright, Joseph C. Ward, Thomas C. McLean, Sophie Forrest, Terry Jackson, Tobias J. Tuthill, David J. Rowlands, Nicola J. Stonehouse
Genetic economy in picornaviruses: Foot-and-mouth disease virus replication exploits alternative precursor cleavage pathways
www.plospathogens.org
www.plospathogens.org
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q
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7.4999 0 0 6.6659 212.1448 594.822 cm
BT
/F6 1 Tf
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Q
q
1 j
1 J
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7.4999 0 0 6.6659 485.0078 581.8393 cm
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Q
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5.8393 0 Td
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1.0148 0 Td
(vRNA)Tj
2.7156 0 Td
(replication)Tj
4.5241 0 Td
(without)Tj
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(the)Tj
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(infectious)Tj
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(six)Tj
1.3153 0 Td
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(were)Tj
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(the)Tj
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(copies)Tj
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1.0148 0 Td
(3B)Tj
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(either)Tj
2.5341 0 Td
(deleted)Tj
-34.5427 -1.3039 Td
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/F12 1 Tf
( )Tj
/F6 1 Tf
(3B1,)Tj
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2.9083 0 Td
( )Tj
/F6 1 Tf
(3B2)Tj
2.3414 0 Td
(and)Tj
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1.7291 0 Td
( )Tj
/F6 1 Tf
(3B3\),)Tj
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(point)Tj
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3.7927 0 Td
(to)Tj
1.0204 0 Td
(phenylalanine)Tj
5.8451 0 Td
([Y3F]\))Tj
2.8743 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(tyrosine)Tj
3.4526 0 Td
(residue)Tj
3.1181 0 Td
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3.4922 0 Td
(3)Tj
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(\(3B1)Tj
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 496.233 545.4992 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(Y3F)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 508.4787 541.0771 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(,)Tj
0.4422 0 Td
(3B2)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 528.2645 545.4992 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(Y3F)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 542.6645 541.0771 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(and)Tj
-34.2649 -1.2982 Td
(3B3)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 215.3196 532.5165 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(Y3F)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 227.5653 528.0944 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
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(\))Tj
0.5555 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8255 0 Td
(1A)Tj
0 g
(\).)Tj
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1.9842 0 Td
(tyrosine)Tj
3.4526 0 Td
(serves)Tj
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(as)Tj
1.0148 0 Td
(the)Tj
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(acceptor)Tj
3.6226 0 Td
(site)Tj
1.5704 0 Td
(for)Tj
1.3833 0 Td
(3D)Tj
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 454.0535 532.5165 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(pol)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 463.5212 528.0944 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(-mediated)Tj
4.2916 0 Td
(uridylation)Tj
4.6714 0 Td
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(3B)Tj
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1.0262 0 Td
(generate)Tj
3.6056 0 Td
(the)Tj
1.4684 0 Td
(replication)Tj
4.524 0 Td
(primer)Tj
2.9934 0 Td
(VPg-pUpU.)Tj
5.0173 0 Td
(Mutation)Tj
3.9968 0 Td
(to)Tj
1.0262 0 Td
(phenylalanine)Tj
5.8392 0 Td
(renders)Tj
3.2485 0 Td
(3B)Tj
1.2756 0 Td
(unable)Tj
-34.0212 -1.2982 Td
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1.0262 0 Td
(act)Tj
1.3719 0 Td
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1.0148 0 Td
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(primer)Tj
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1.3889 0 Td
(replication)Tj
4.5241 0 Td
([)Tj
0.83 0.64 0.02 0 k
(40)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(41)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3946 0 Td
(43)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.4003 0 Td
(49)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3947 0 Td
(52)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3946 0 Td
(59)Tj
0 g
(].)Tj
1.7405 0 Td
(Alongside,)Tj
4.4729 0 Td
(a)Tj
0.652 0 Td
(seventh)Tj
3.2598 0 Td
(replicon)Tj
3.5263 0 Td
(was)Tj
1.6951 0 Td
(gen-)Tj
-35.6369 -1.2983 Td
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2.6986 0 Td
(in)Tj
1.0318 0 Td
(which)Tj
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(both)Tj
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(3B1)Tj
1.7518 0 Td
(and)Tj
1.7291 0 Td
(3B2)Tj
1.7518 0 Td
(were)Tj
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(deleted)Tj
3.0897 0 Td
(\()Tj
/F12 1 Tf
( )Tj
/F6 1 Tf
(3B1+2\))Tj
4.0762 0 Td
(to)Tj
1.0261 0 Td
(determine)Tj
4.3199 0 Td
(if)Tj
0.7767 0 Td
(retaining)Tj
3.8438 0 Td
(only)Tj
1.9785 0 Td
(3B3)Tj
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3.9174 0 Td
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(replication.)Tj
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1.4683 0 Td
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-33.6356 -1.3039 Td
(replicons)Tj
3.8835 0 Td
(and)Tj
1.7291 0 Td
(transfected)Tj
4.6205 0 Td
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1.8425 0 Td
(BHK-21)Tj
3.5432 0 Td
(cells.)Tj
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1.1112 0 Td
(addition,)Tj
3.8211 0 Td
(cells)Tj
1.9219 0 Td
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4.6204 0 Td
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1.9956 0 Td
(RNA)Tj
-33.3522 -1.2982 Td
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3.2145 0 Td
(from)Tj
2.2054 0 Td
(a)Tj
0.6519 0 Td
(wild-type)Tj
3.9912 0 Td
(replicon)Tj
3.5263 0 Td
(and)Tj
1.7291 0 Td
(from)Tj
2.2053 0 Td
(a)Tj
0.652 0 Td
(replication-defective)Tj
8.4074 0 Td
(replicon)Tj
3.5263 0 Td
(with)Tj
1.9955 0 Td
(mutations)Tj
4.2803 0 Td
(at)Tj
-36.3852 -1.2983 Td
(the)Tj
1.4684 0 Td
(active)Tj
2.5228 0 Td
(site)Tj
1.5704 0 Td
(of)Tj
1.0148 0 Td
(3D)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 277.8519 441.5244 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(pol)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 289.5874 437.1023 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\(3D)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 305.0645 441.5244 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(pol)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 314.5889 437.1023 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(-GNN\),)Tj
3.3221 0 Td
(which)Tj
2.6532 0 Td
(served)Tj
2.778 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(control)Tj
3.1181 0 Td
(for)Tj
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(translation)Tj
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2.2053 0 Td
(the)Tj
1.4684 0 Td
(input)Tj
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(RNA)Tj
2.262 0 Td
(replication)Tj
4.5184 0 Td
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(fluorescence)Tj
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(mCherry)Tj
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1.9729 0 Td
(a)Tj
0.6576 0 Td
(24)Tj
1.1679 0 Td
(hour)Tj
2.1543 0 Td
(period,)Tj
3.0614 0 Td
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1.9956 0 Td
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3.1406 0 Td
(replication)Tj
4.5241 0 Td
(shown)Tj
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1.4683 0 Td
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(8)Tj
0.6917 0 Td
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2.5171 0 Td
(post-transfection,)Tj
7.251 0 Td
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1.4683 0 Td
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(maximal)Tj
3.7077 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(S1)Tj
1.5137 0 Td
(Fig)Tj
0 g
(\).)Tj
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1.8652 0 Td
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3.651 0 Td
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2.279 0 Td
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1.542 0 Td
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1.7802 0 Td
(identical)Tj
3.6566 0 Td
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4.439 0 Td
(either)Tj
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-34.4349 -1.2983 Td
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5.1874 0 Td
(or)Tj
1.0941 0 Td
(fluorescent)Tj
4.6431 0 Td
(cell)Tj
1.559 0 Td
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3.7757 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.474 0 Td
(latter)Tj
2.2904 0 Td
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(shown)Tj
2.846 0 Td
(here)Tj
1.9672 0 Td
([)Tj
0.83 0.64 0.02 0 k
(60)Tj
0 g
(].)Tj
-26.2202 -1.2982 Td
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1.7858 0 Td
(results)Tj
2.8063 0 Td
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1.0148 0 Td
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2.2564 0 Td
(experiments)Tj
5.1362 0 Td
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1.4513 0 Td
(shown)Tj
2.846 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(Fig)Tj
1.4796 0 Td
(1B)Tj
0 g
(.)Tj
1.5024 0 Td
(Consistent)Tj
4.4957 0 Td
(with)Tj
1.9956 0 Td
(previous)Tj
3.651 0 Td
(studies)Tj
2.9877 0 Td
([)Tj
0.83 0.64 0.02 0 k
(49)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
-35.6425 -1.304 Td
(55)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3946 0 Td
(56)Tj
0 g
(],)Tj
1.7348 0 Td
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1.2756 0 Td
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1.0375 0 Td
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(replication)Tj
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4.2462 0 Td
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1.0205 0 Td
(the)Tj
1.474 0 Td
(wild-)Tj
-34.2592 -1.2982 Td
(type)Tj
1.9105 0 Td
(control)Tj
3.1238 0 Td
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2.3187 0 Td
(deletion)Tj
3.4639 0 Td
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1.0147 0 Td
(3B1)Tj
1.7518 0 Td
(\()Tj
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( )Tj
/F6 1 Tf
(3B1\))Tj
3.0217 0 Td
(or)Tj
1.0999 0 Td
(3B2)Tj
1.7461 0 Td
(\()Tj
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( )Tj
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(3B2\),)Tj
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(or)Tj
1.0998 0 Td
(both)Tj
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(3B1)Tj
1.7518 0 Td
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(3B2)Tj
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(\()Tj
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( )Tj
/F6 1 Tf
(3B1)Tj
-34.6277 -1.2983 Td
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1.8425 0 Td
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1.1055 0 Td
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(3B3)Tj
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3.4469 0 Td
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(100-fold,)Tj
3.7927 0 Td
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1.0205 0 Td
(a)Tj
-36.2491 -1.2983 Td
(level)Tj
2.0126 0 Td
(comparable)Tj
4.9039 0 Td
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1.0261 0 Td
(the)Tj
1.4683 0 Td
(3D)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 306.2551 311.5275 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(pol)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 315.7228 307.1055 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
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(-GNN)Tj
2.7609 0 Td
(replication-deficient)Tj
8.3395 0 Td
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3.1237 0 Td
(\(i.e.)Tj
1.7008 0 Td
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1.1111 0 Td
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3.8211 0 Td
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4.388 0 Td
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3.5263 0 Td
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-35.5008 -1.2982 Td
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3.9912 0 Td
(replicon)Tj
3.5206 0 Td
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1.7291 0 Td
(the)Tj
1.474 0 Td
(replicons)Tj
3.8833 0 Td
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3.2372 0 Td
(individual)Tj
4.2859 0 Td
(non-uridylatable)Tj
6.9165 0 Td
(Y3F)Tj
1.8539 0 Td
(mutations)Tj
4.2803 0 Td
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-35.172 -1.2983 Td
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1.6554 0 Td
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1.0148 0 Td
(the)Tj
1.4684 0 Td
(3B)Tj
1.2755 0 Td
(molecules.)Tj
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1.9956 0 Td
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3.651 0 Td
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3.447 0 Td
(that)Tj
1.7801 0 Td
(dele-)Tj
-34.52 -1.3039 Td
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1.8425 0 Td
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1.0148 0 Td
(3B3,)Tj
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1.5534 0 Td
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1.576 0 Td
(3B1)Tj
1.7518 0 Td
(or)Tj
1.0942 0 Td
(3B2,)Tj
1.9785 0 Td
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0.8504 0 Td
(detrimental)Tj
4.8755 0 Td
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1.389 0 Td
(vRNA)Tj
2.7156 0 Td
(replication.)Tj
4.7451 0 Td
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4.0819 0 Td
(mutations)Tj
4.2803 0 Td
(that)Tj
-35.7219 -1.2983 Td
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2.8857 0 Td
(individual)Tj
4.2859 0 Td
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2.7213 0 Td
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1.0147 0 Td
(3B)Tj
1.2755 0 Td
(non-functional)Tj
6.2646 0 Td
(\(including)Tj
4.3823 0 Td
(3B3\))Tj
2.0863 0 Td
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1.2586 0 Td
(not)Tj
1.5703 0 Td
(inhibit)Tj
2.9027 0 Td
(replication.)Tj
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Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 203.9811 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
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4.3323 0 Td
(at)Tj
1.0488 0 Td
(the)Tj
1.5921 0 Td
(C-terminus)Tj
5.0599 0 Td
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1.0441 0 Td
(3B3)Tj
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(important)Tj
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(FMDV)Tj
3.0378 0 Td
(replication)Tj
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Q
q
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