10
5
D
Virus: NL4-3 and NL4-3nef-
Target cells: TZM-bl
T2
0
4E
10
Z1
3E
1
2F
5
E5
1
G sul
oa
ph
ts
er
um
sC
D
4
B1
2
2G
12
17
B
1X
0
ex
IC50
fold increase
The Nef induced increase of resistance to
neutralization is highly specific for 2F5 and 4E10
no Nef
Clade B Nef
Clade C Nef
SIV AGM Nef
100
50
10
5
AG
M
V
SI
IV
-1
C
la
de
C
B
la
de
H
Nef from:
C
4E10 (µg/ml)
10 2
-1
10 1
N
10 0
IV
10 -2 10 -1
no
ef
1X
H
0
15
IC50
fold increase
Residual infectivity (%)
Nef alleles derived from clade C and from SIV have a
similar effect on HIV-1 sensitivity to 2F5 and 4E10
This activity of Nef is highly conserved
10 0
10 1
4E10 (µg/ml)
10 2
1X
The activity is not unique to
primate lentiviruses
ag
10 -2 10 -1
5
gl
yc
og
10
IN
ef
0
15
H
IV
-1
50
20
N
ef
100
no
Vector
LAI Nef
MLV glycogag
IC50
fold increase
Residual infectivity (%)
Glycosylated gag from MoMLV has the same
activity on HIV-1 neutralization
Nef inhibits capture of HIV-1 by 2F5 and 4E10,
but not by Z13e1, which also targets MPER
25
20
4
15
10
2
Env+
2F5
0
Env-
Nef-
0.8
0.6
0.4
0.2
0.0
Env+
Nef+
1.0
µU RT
0
5
HIV-1 captured
µU RT
HIV-1 captured
6
Env+
Z13e1
Env-
4E10
Env-