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char = d;code = 100
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char = o;code = 111
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char = a;code = 97
char = l;code = 108
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char = c;code = 99
char = h;code = 104
char = a;code = 97
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char = a;code = 97
char = c;code = 99
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char = e;code = 101
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char = z;code = 122
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = R;code = 82
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char = s;code = 115
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char = o;code = 111
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char = ;code = 32
char = E;code = 69
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = V;code = 86
char = P;code = 80
char = 3;code = 51
char = 5;code = 53
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
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char = d;code = 100
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = .;code = 46
result sql = Structural and functional characterization of Reston Ebola virus VP35 interferon inhibitory domain.
Structural and functional characterization of Reston Ebola virus VP35 interferon inhibitory domain.
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char = o;code = 111
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char = s;code = 115
char = e;code = 101
char = s;code = 115
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char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
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char = t;code = 116
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char = e;code = 101
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char = a;code = 97
char = g;code = 103
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = e;code = 101
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char = l;code = 108
char = ;code = 32
char = h;code = 104
char = e;code = 101
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char = r;code = 114
char = h;code = 104
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char = e;code = 101
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char = ;code = 32
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char = o;code = 111
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char = f;code = 102
char = a;code = 97
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = R;code = 82
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = o;code = 111
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char = E;code = 69
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = a;code = 97
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char = v;code = 118
char = i;code = 105
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char = u;code = 117
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = E;code = 69
char = B;code = 66
char = O;code = 79
char = V;code = 86
char = );code = 41
char = ;code = 32
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char = t;code = 116
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char = ;code = 32
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char = h;code = 104
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char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
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char = o;code = 111
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char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = s;code = 115
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char = d;code = 100
char = e;code = 101
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char = p;code = 112
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char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
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char = t;code = 116
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char = a;code = 97
char = t;code = 116
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char = E;code = 69
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char = a;code = 97
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char = e;code = 101
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char = e;code = 101
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char = i;code = 105
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char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
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char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = .;code = 46
char = ;code = 32
char = P;code = 80
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char = s;code = 115
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char = e;code = 101
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char = a;code = 97
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char = s;code = 115
char = o;code = 111
char = ;code = 32
char = s;code = 115
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char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = B;code = 66
char = O;code = 79
char = V;code = 86
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char = i;code = 105
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char = s;code = 115
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = v;code = 118
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char = a;code = 97
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char = ;code = 32
char = i;code = 105
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char = i;code = 105
char = b;code = 98
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char = s;code = 115
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char = i;code = 105
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char = n;code = 110
char = a;code = 97
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char = m;code = 109
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char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = Z;code = 90
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = E;code = 69
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = Z;code = 90
char = E;code = 69
char = B;code = 66
char = O;code = 79
char = V;code = 86
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char = ;code = 32
char = o;code = 111
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char = ;code = 32
char = M;code = 77
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char = g;code = 103
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char = i;code = 105
char = r;code = 114
char = u;code = 117
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = V;code = 86
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = c;code = 99
char = o;code = 111
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char = e;code = 101
char = d;code = 100
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char = V;code = 86
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char = i;code = 105
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char = p;code = 112
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char = m;code = 109
char = ;code = 32
char = R;code = 82
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char = B;code = 66
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char = ;code = 32
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char = c;code = 99
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char = d;code = 100
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char = e;code = 101
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char = e;code = 101
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char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = b;code = 98
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char = d;code = 100
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char = m;code = 109
char = a;code = 97
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char = I;code = 73
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char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = u;code = 117
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = e;code = 101
char = x;code = 120
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = B;code = 66
char = O;code = 79
char = V;code = 86
char = ;code = 32
char = V;code = 86
char = P;code = 80
char = 3;code = 51
char = 5;code = 53
char = ;code = 32
char = I;code = 73
char = I;code = 73
char = D;code = 68
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = i;code = 105
char = f;code = 102
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 1;code = 49
char = .;code = 46
char = 7;code = 55
char = 1;code = 49
char = -;code = 45
char = A;code = 65
char = ;code = 32
char = c;code = 99
char = r;code = 114
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = B;code = 66
char = O;code = 79
char = V;code = 86
char = ;code = 32
char = V;code = 86
char = P;code = 80
char = 3;code = 51
char = 5;code = 53
char = ;code = 32
char = I;code = 73
char = I;code = 73
char = D;code = 68
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = Z;code = 90
char = E;code = 69
char = B;code = 66
char = O;code = 79
char = V;code = 86
char = ;code = 32
char = V;code = 86
char = P;code = 80
char = 3;code = 51
char = 5;code = 53
char = ;code = 32
char = I;code = 73
char = I;code = 73
char = D;code = 68
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = b;code = 98
char = a;code = 97
char = c;code = 99
char = k;code = 107
char = b;code = 98
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = .;code = 46
char = m;code = 109
char = .;code = 46
char = s;code = 115
char = .;code = 46
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 6;code = 54
char = 4;code = 52
char = ;code = 32
char = A;code = 65
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = k;code = 107
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = V;code = 86
char = P;code = 80
char = 3;code = 51
char = 5;code = 53
char = ;code = 32
char = I;code = 73
char = I;code = 73
char = D;code = 68
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = k;code = 107
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = w;code = 119
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = B;code = 66
char = O;code = 79
char = V;code = 86
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = Z;code = 90
char = E;code = 69
char = B;code = 66
char = O;code = 79
char = V;code = 86
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = k;code = 107
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = -;code = 45
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = u;code = 117
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = -;code = 45
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = -;code = 45
char = b;code = 98
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = Z;code = 90
char = E;code = 69
char = B;code = 66
char = O;code = 79
char = V;code = 86
char = ;code = 32
char = V;code = 86
char = P;code = 80
char = 3;code = 51
char = 5;code = 53
char = ;code = 32
char = I;code = 73
char = I;code = 73
char = D;code = 68
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = B;code = 66
char = O;code = 79
char = V;code = 86
char = ;code = 32
char = V;code = 86
char = P;code = 80
char = 3;code = 51
char = 5;code = 53
char = ;code = 32
char = I;code = 73
char = I;code = 73
char = D;code = 68
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = V;code = 86
char = P;code = 80
char = 3;code = 51
char = 5;code = 53
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = m;code = 109
char = u;code = 117
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
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result sql = Ebolaviruses are causative agents of lethal hemorrhagic fever in humans and nonhuman primates. Among the filoviruses characterized thus far, Reston Ebola virus (REBOV) is the only Ebola virus that is nonpathogenic to humans despite the fact that REBOV can cause lethal disease in nonhuman primates. Previous studies also suggest that REBOV is less effective at inhibiting host innate immune responses than Zaire Ebola virus (ZEBOV) or Marburg virus. Virally encoded VP35 protein is critical for immune suppression, but an understanding of the relative contributions of VP35 proteins from REBOV and other filoviruses is currently lacking. In order to address this question, we characterized the REBOV VP35 interferon inhibitory domain (IID) using structural, biochemical, and virological studies. These studies reveal differences in double-stranded RNA binding and interferon inhibition between the two species. These observed differences are likely due to increased stability and loss of flexibility in REBOV VP35 IID, as demonstrated by thermal shift stability assays. Consistent with this finding, the 1.71-A crystal structure of REBOV VP35 IID reveals that it is highly similar to that of ZEBOV VP35 IID, with an overall backbone r.m.s.d. of 0.64 A, but contains an additional helical element at the linker between the two subdomains of VP35 IID. Mutations near the linker, including swapping sequences between REBOV and ZEBOV, reveal that the linker sequence has limited tolerance for variability. Together with the previously solved ligand-free and double-stranded-RNA-bound forms of ZEBOV VP35 IID structures, our current studies on REBOV VP35 IID reinforce the importance of VP35 in immune suppression. Functional differences observed between REBOV and ZEBOV VP35 proteins may contribute to observed differences in pathogenicity, but these are unlikely to be the major determinant. However, the high level of similarity in structure and the low tolerance for sequence variability, coupled with the multiple critical roles played by Ebola virus VP35 proteins, highlight the viability of VP35 as a potential target for therapeutic development.

Publication: J. Mol. Biol. 2010 Jun 11 ;399(3)::347-57. :doi: 10.1016/j.jmb.2010.04.022.
Publication Date: 2010 Jun 11
Study Author(s): Leung, Daisy W;Shabman, Reed S;Farahbakhsh, Mina;Prins, Kathleen C;Borek, Dominika M;Wang, Tianjiao;Mühlberger, Elke;Basler, Christopher F;Amarasinghe, Gaya K;
Institution: Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
Shortcut link to this study:
Ebolaviruses are causative agents of lethal hemorrhagic fever in humans and nonhuman primates. Among the filoviruses characterized thus far, Reston Ebola virus (REBOV) is the only Ebola virus that is nonpathogenic to humans despite the fact that REBOV can cause lethal disease in nonhuman primates. Previous studies also suggest that REBOV is less effective at inhibiting host innate immune responses than Zaire Ebola virus (ZEBOV) or Marburg virus. Virally encoded VP35 protein is critical for immune suppression, but an understanding of the relative contributions of VP35 proteins from REBOV and other filoviruses is currently lacking. In order to address this question, we characterized the REBOV VP35 interferon inhibitory domain (IID) using structural, biochemical, and virological studies. These studies reveal differences in double-stranded RNA binding and interferon inhibition between the two species. These observed differences are likely due to increased stability and loss of flexibility in REBOV VP35 IID, as demonstrated by thermal shift stability assays. Consistent with this finding, the 1.71-A crystal structure of REBOV VP35 IID reveals that it is highly similar to that of ZEBOV VP35 IID, with an overall backbone r.m.s.d. of 0.64 A, but contains an additional helical element at the linker between the two subdomains of VP35 IID. Mutations near the linker, including swapping sequences between REBOV and ZEBOV, reveal that the linker sequence has limited tolerance for variability. Together with the previously solved ligand-free and double-stranded-RNA-bound forms of ZEBOV VP35 IID structures, our current studies on REBOV VP35 IID reinforce the importance of VP35 in immune suppression. Functional differences observed between REBOV and ZEBOV VP35 proteins may contribute to observed differences in pathogenicity, but these are unlikely to be the major determinant. However, the high level of similarity in structure and the low tolerance for sequence variability, coupled with the multiple critical roles played by Ebola virus VP35 proteins, highlight the viability of VP35 as a potential target for therapeutic development.
PMID: 20399790

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