Overview of the expression, binding and functional parameters of the CCR5 mutants*
. | Allelic frequency (estimation from available data) . | Surface expression (2D7 MCF) . | MIP-1β binding PIC50 −Log(M) ± SEM . | MIP-1β functional response pEC50 −Log(M) ± SEM . | HIV-1 infection . |
---|---|---|---|---|---|
CCR5 | 1463 | 9.12 ± 0.15 | 8.57 ± 0.15 | ++ | |
I12L | Afro-Americans: 0.000 | 1469 | 9.14 ± 0.07 | 8.18 ± 0.19 | ++ |
Caucasians: 0.003 | |||||
C20S | Afro-Americans: 0.000 | 318.5 | nm | >6 | ++ |
Caucasians: 0.003 | |||||
A29S | Afro-Americans: 0.015 | 997 | nm | 6.70 ± 0.44 | ++ |
I42F | Afro-Americans: 0.007 | 1130 | nd | 8.17 ± 0.33 | ++ |
Caucasians: 0.001 | |||||
L55Q | Afro-Americans: 0.007 | 823 | 9.28 ± 0.05 | 7.53 ± 0.31 | ++ |
Caucasians: 0.041 | |||||
R60S | Afro-Americans: 0.013 | 1030 | nd | 8.07 ± 0.25 | ++ |
A73V | Afro-Americans: 0.000 | 481 | nd | 7.73 ± 0.40 | ++ |
Caucasians: 0.002 | |||||
C101X | Afro-Americans: 0.014 | 5 | nm | >6 | − |
C178R | Asians | 8 | nm | >6 | + |
Δ32 | Caucasians: 0.100 | 4 | nm | >6 | − |
Africans: 0.000 | |||||
S215L | Afro-Americans: 0.010 | 941 | 9.16 ± 0.06 | 8.3 ± 0.28 | ++ |
R223Q | Caucasians: 0.013 | 1153 | N.D. | 8.35 ± 0.07 | + |
ΔK228 | Afro-Americans: 0.000 | 2373 | 8.99 ± 0.07 | 8.9 ± 0.28 | ++ |
Caucasians: 0.002 | |||||
FS299 | Asians: 0.035 | 14.7 | nm | >6 | + |
G301V | Afro-Americans: 0.000 | 1542 | 8.96 ± 0.05 | 8.45 ± 0.07 | ++ |
Caucasians: 0.011 | |||||
A335V | Afro-Americans: 0.025 | 1504 | nd | 8.55 ± 0.07 | ++ |
Caucasians: 0.006 | |||||
Y339F | Afro-Americans: 0.026 | 1916 | nd | 8.6 ± 0.05 | ++ |
Caucasians: 0.000 |
. | Allelic frequency (estimation from available data) . | Surface expression (2D7 MCF) . | MIP-1β binding PIC50 −Log(M) ± SEM . | MIP-1β functional response pEC50 −Log(M) ± SEM . | HIV-1 infection . |
---|---|---|---|---|---|
CCR5 | 1463 | 9.12 ± 0.15 | 8.57 ± 0.15 | ++ | |
I12L | Afro-Americans: 0.000 | 1469 | 9.14 ± 0.07 | 8.18 ± 0.19 | ++ |
Caucasians: 0.003 | |||||
C20S | Afro-Americans: 0.000 | 318.5 | nm | >6 | ++ |
Caucasians: 0.003 | |||||
A29S | Afro-Americans: 0.015 | 997 | nm | 6.70 ± 0.44 | ++ |
I42F | Afro-Americans: 0.007 | 1130 | nd | 8.17 ± 0.33 | ++ |
Caucasians: 0.001 | |||||
L55Q | Afro-Americans: 0.007 | 823 | 9.28 ± 0.05 | 7.53 ± 0.31 | ++ |
Caucasians: 0.041 | |||||
R60S | Afro-Americans: 0.013 | 1030 | nd | 8.07 ± 0.25 | ++ |
A73V | Afro-Americans: 0.000 | 481 | nd | 7.73 ± 0.40 | ++ |
Caucasians: 0.002 | |||||
C101X | Afro-Americans: 0.014 | 5 | nm | >6 | − |
C178R | Asians | 8 | nm | >6 | + |
Δ32 | Caucasians: 0.100 | 4 | nm | >6 | − |
Africans: 0.000 | |||||
S215L | Afro-Americans: 0.010 | 941 | 9.16 ± 0.06 | 8.3 ± 0.28 | ++ |
R223Q | Caucasians: 0.013 | 1153 | N.D. | 8.35 ± 0.07 | + |
ΔK228 | Afro-Americans: 0.000 | 2373 | 8.99 ± 0.07 | 8.9 ± 0.28 | ++ |
Caucasians: 0.002 | |||||
FS299 | Asians: 0.035 | 14.7 | nm | >6 | + |
G301V | Afro-Americans: 0.000 | 1542 | 8.96 ± 0.05 | 8.45 ± 0.07 | ++ |
Caucasians: 0.011 | |||||
A335V | Afro-Americans: 0.025 | 1504 | nd | 8.55 ± 0.07 | ++ |
Caucasians: 0.006 | |||||
Y339F | Afro-Americans: 0.026 | 1916 | nd | 8.6 ± 0.05 | ++ |
Caucasians: 0.000 |
The allelic frequencies of each mutant were estimated from the data available in the populations studied so far.10,25 26Surface expression of the mutant receptors in transfected CHO-K1 cells is presented as the mean channel fluorescence (MCF) using the 2D7 monoclonal antibody (Mab). The binding (pIC50) and functional (pEC50) parameters are given, as well as the ability of the mutants to support human immunodeficiency virus (HIV) infection. Means and errors (SEM) were calculated from at least two independent experiments. nm, not measurable given the low binding affinity; nd, not determined.