TY - JOUR
T1 - Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes
AU - Scopelliti, Fernanda
AU - Pollicita, Michela
AU - Ceccherini-Silberstein, Francesca
AU - Di Santo, Fabiola
AU - Surdo, Matteo
AU - Aquaro, Stefano
AU - Perno, Carlo Federico
PY - 2011/11
Y1 - 2011/11
N2 - The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810, IN2, and IN5) was investigated in primary human macrophages, PBMC and C8166-lymphocytic T cells, in order to determine their relative potency and efficacy in different cellular systems of HIV infection. Raltegravir showed better protective efficacy in all cell types; MK-2048, L870,810 and IN5 showed a potent anti-HIV-1 activity in macrophages, while in lymphocytes only MK-2048 and L870,810 showed an inhibitory effect comparable to raltegravir. IN2 was a poorly effective anti-HIV-1 compound in all cellular systems. All effective integrase inhibitors exhibited a potent antiviral activity against both X4 and R5 HIV-1 strains. In general, raltegravir, MK-2048, L870,810 and IN5 showed anti HIV activity similar or slightly higher in macrophages compared to PBMC and C8166 T cells: for MK-2048, the EC 50 was 0.4, 0.9, 11.5nM in macrophages, in PBMCs and T cells, respectively; for L870,810, the EC 50 was 1.5, 14.3, and 10.6nM, respectively; for IN5 the EC 50 was 0.5, 13.7, and 5.7nM, respectively.
AB - The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810, IN2, and IN5) was investigated in primary human macrophages, PBMC and C8166-lymphocytic T cells, in order to determine their relative potency and efficacy in different cellular systems of HIV infection. Raltegravir showed better protective efficacy in all cell types; MK-2048, L870,810 and IN5 showed a potent anti-HIV-1 activity in macrophages, while in lymphocytes only MK-2048 and L870,810 showed an inhibitory effect comparable to raltegravir. IN2 was a poorly effective anti-HIV-1 compound in all cellular systems. All effective integrase inhibitors exhibited a potent antiviral activity against both X4 and R5 HIV-1 strains. In general, raltegravir, MK-2048, L870,810 and IN5 showed anti HIV activity similar or slightly higher in macrophages compared to PBMC and C8166 T cells: for MK-2048, the EC 50 was 0.4, 0.9, 11.5nM in macrophages, in PBMCs and T cells, respectively; for L870,810, the EC 50 was 1.5, 14.3, and 10.6nM, respectively; for IN5 the EC 50 was 0.5, 13.7, and 5.7nM, respectively.
KW - HIV
KW - Integrase inhibitors
KW - Lymphocytes
KW - Macrophages
KW - PBMC
UR - http://www.scopus.com/inward/record.url?scp=80054854717&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054854717&partnerID=8YFLogxK
U2 - 10.1016/j.antiviral.2011.08.008
DO - 10.1016/j.antiviral.2011.08.008
M3 - Article
C2 - 21867733
AN - SCOPUS:80054854717
VL - 92
SP - 255
EP - 261
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 2
ER -