|
|
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result sql = Valacyclovir combined with artesunate or rapamycin improves the outcome of herpes simplex virus encephalitis in mice compared to antiviral therapy alone.
Valacyclovir combined with artesunate or rapamycin improves the outcome of herpes simplex virus encephalitis in mice compared to antiviral therapy alone.char = D;code = 68
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result sql = Despite antiviral therapy, the mortality rate of herpes simplex virus encephalitis (HSE) remains high and many surviving patients harbor neurological sequelae. Although viral replication is responsible for substantial neurological damages, an exaggerated inflammatory response could also contribute to this process. Artesunate (ART) and rapamycin (RAPA) have shown some benefits in the treatment of herpes simplex virus infections. Herein, we evaluated the benefit of combining ART or RAPA with valacyclovir (VACV) in a murine model of HSE. Infected mice were treated with VACV (1mg/mL in drinking water) from day 3 post-infection (p.i.) combined or not with daily intraperitoneal administration of ART (30mg/kg) or RAPA (20mg/kg) from days 4 to 13 p.i. Viral load, infectious titers, cytokine and chemokine levels were measured in brain homogenates on days 5, 7 and 9. The survival rates of mice treated with VACV and ART or RAPA were higher than with VACV alone (71.9% versus 43.2% for ART and 66.7% versus 43.2% for RAPA; both P⩽0.05) but no significant difference was seen in the brain viral loads. Levels of IL-1β, IL-2 (both P⩽0.05), IL-6, IFN-γ (both P⩽0.01), CCL2 (P⩽0.01), CCL3 and CCL4 (both P⩽0.05) were reduced in mice treated with VACV combined with ART versus VACV alone. Levels of IL-6, IL-1β and IFN-γ slightly increased on day 7 in mice treated with VACV combined with RAPA compared to VACV alone and then decreased on day 9. Our results suggest that immunomodulatory compounds such as ART or RAPA could benefit antiviral therapy in HSE.
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char = x;code = 120
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 = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = .;code = 46
result sql = Valacyclovir combined with artesunate or rapamycin improves the outcome of herpes simplex virus encephalitis in mice compared to antiviral therapy alone.
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = p;code = 112
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = x;code = 120
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 = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = H;code = 72
char = S;code = 83
char = E;code = 69
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = a;code = 97
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = A;code = 65
char = R;code = 82
char = T;code = 84
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = a;code = 97
char = m;code = 109
char = y;code = 121
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = A;code = 65
char = P;code = 80
char = A;code = 65
char = );code = 41
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = f;code = 102
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
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 = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = p;code = 112
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = x;code = 120
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 = i;code = 105
char = n;code = 110
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = f;code = 102
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
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char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = A;code = 65
char = R;code = 82
char = T;code = 84
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = R;code = 82
char = A;code = 65
char = P;code = 80
char = A;code = 65
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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char = v;code = 118
char = a;code = 97
char = l;code = 108
char = a;code = 97
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = V;code = 86
char = A;code = 65
char = C;code = 67
char = V;code = 86
char = );code = 41
char = ;code = 32
char = i;code = 105
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char = ;code = 32
char = a;code = 97
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char = m;code = 109
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char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = H;code = 72
char = S;code = 83
char = E;code = 69
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = m;code = 109
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char = c;code = 99
char = e;code = 101
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char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = e;code = 101
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char = h;code = 104
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char = V;code = 86
char = A;code = 65
char = C;code = 67
char = V;code = 86
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = m;code = 109
char = g;code = 103
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char = m;code = 109
char = L;code = 76
char = ;code = 32
char = i;code = 105
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char = ;code = 32
char = d;code = 100
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char = n;code = 110
char = k;code = 107
char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = f;code = 102
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char = m;code = 109
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char = a;code = 97
char = y;code = 121
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char = 3;code = 51
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char = p;code = 112
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char = c;code = 99
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = A;code = 65
char = R;code = 82
char = T;code = 84
char = ;code = 32
char = (;code = 40
char = 3;code = 51
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char = m;code = 109
char = g;code = 103
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char = k;code = 107
char = g;code = 103
char = );code = 41
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = R;code = 82
char = A;code = 65
char = P;code = 80
char = A;code = 65
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = 0;code = 48
char = m;code = 109
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char = /;code = 47
char = k;code = 107
char = g;code = 103
char = );code = 41
char = ;code = 32
char = f;code = 102
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char = d;code = 100
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char = 4;code = 52
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = 1;code = 49
char = 3;code = 51
char = ;code = 32
char = p;code = 112
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char = i;code = 105
char = .;code = 46
char = ;code = 32
char = V;code = 86
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char = l;code = 108
char = ;code = 32
char = l;code = 108
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char = t;code = 116
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char = ,;code = 44
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char = d;code = 100
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char = c;code = 99
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char = ;code = 32
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char = d;code = 100
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result sql = Despite antiviral therapy, the mortality rate of herpes simplex virus encephalitis (HSE) remains high and many surviving patients harbor neurological sequelae. Although viral replication is responsible for substantial neurological damages, an exaggerated inflammatory response could also contribute to this process. Artesunate (ART) and rapamycin (RAPA) have shown some benefits in the treatment of herpes simplex virus infections. Herein, we evaluated the benefit of combining ART or RAPA with valacyclovir (VACV) in a murine model of HSE. Infected mice were treated with VACV (1mg/mL in drinking water) from day 3 post-infection (p.i.) combined or not with daily intraperitoneal administration of ART (30mg/kg) or RAPA (20mg/kg) from days 4 to 13 p.i. Viral load, infectious titers, cytokine and chemokine levels were measured in brain homogenates on days 5, 7 and 9. The survival rates of mice treated with VACV and ART or RAPA were higher than with VACV alone (71.9% versus 43.2% for ART and 66.7% versus 43.2% for RAPA; both P⩽0.05) but no significant difference was seen in the brain viral loads. Levels of IL-1β, IL-2 (both P⩽0.05), IL-6, IFN-γ (both P⩽0.01), CCL2 (P⩽0.01), CCL3 and CCL4 (both P⩽0.05) were reduced in mice treated with VACV combined with ART versus VACV alone. Levels of IL-6, IL-1β and IFN-γ slightly increased on day 7 in mice treated with VACV combined with RAPA compared to VACV alone and then decreased on day 9. Our results suggest that immunomodulatory compounds such as ART or RAPA could benefit antiviral therapy in HSE.
Publication: Antiviral Res. 2015 Nov;123():105-13.
Publication Date: Nov 2015
Study Author(s): Canivet Coraline C ; Menasria Rafik R ; Rhéaume Chantal C ; Piret Jocelyne J ; Boivin Guy G ;
Institution: Research Center of the CHU of Quebec and Laval University, Quebec City, QC, Canada.
Shortcut link to this study:
Publication Date: Nov 2015
Study Author(s): Canivet Coraline C ; Menasria Rafik R ; Rhéaume Chantal C ; Piret Jocelyne J ; Boivin Guy G ;
Institution: Research Center of the CHU of Quebec and Laval University, Quebec City, QC, Canada.
Shortcut link to this study:
Despite antiviral therapy, the mortality rate of herpes simplex virus encephalitis (HSE) remains high and many surviving patients harbor neurological sequelae. Although viral replication is responsible for substantial neurological damages, an exaggerated inflammatory response could also contribute to this process. Artesunate (ART) and rapamycin (RAPA) have shown some benefits in the treatment of herpes simplex virus infections. Herein, we evaluated the benefit of combining ART or RAPA with valacyclovir (VACV) in a murine model of HSE. Infected mice were treated with VACV (1mg/mL in drinking water) from day 3 post-infection (p.i.) combined or not with daily intraperitoneal administration of ART (30mg/kg) or RAPA (20mg/kg) from days 4 to 13 p.i. Viral load, infectious titers, cytokine and chemokine levels were measured in brain homogenates on days 5, 7 and 9. The survival rates of mice treated with VACV and ART or RAPA were higher than with VACV alone (71.9% versus 43.2% for ART and 66.7% versus 43.2% for RAPA; both P⩽0.05) but no significant difference was seen in the brain viral loads. Levels of IL-1β, IL-2 (both P⩽0.05), IL-6, IFN-γ (both P⩽0.01), CCL2 (P⩽0.01), CCL3 and CCL4 (both P⩽0.05) were reduced in mice treated with VACV combined with ART versus VACV alone. Levels of IL-6, IL-1β and IFN-γ slightly increased on day 7 in mice treated with VACV combined with RAPA compared to VACV alone and then decreased on day 9. Our results suggest that immunomodulatory compounds such as ART or RAPA could benefit antiviral therapy in HSE.
PMID: 26374952
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