Table II. Sequence requirements of HIV-1 Nef for respective functionsa,b.
Residues in NefNL4-3 | Infectivity | PBMC replic. | Pak activation | CD4↓ | MHC-I↓ | Pathogenicity |
---|---|---|---|---|---|---|
MGxxxS(1) |
+ |
+ |
+ |
+ |
+ |
+c |
WL(57) |
+/– |
+ |
– |
+ |
– |
n.d. |
EEEE(62) |
+/– |
+/– |
n.d. |
– |
+ |
+c |
PxxP(72) |
+/– |
+ |
+ |
+/– |
+ |
+/– c,d |
RR(105) |
+/– |
n.d. |
+ |
+/– |
n.d. |
+c,d |
FPD(121) |
+ |
n.d. |
n.d. |
+ |
+ |
n.d. |
EE(154) |
n.d. |
n.d. |
n.d. |
+/– |
n.d. |
n.d. |
LL(164) |
+ |
+ |
n.d. |
+ |
– |
n.d. |
DD(174) | n.d. | n.d. | n.d. | + | – | +d |
a+, required for function; +/–, partially required; –, not required; n.d., not determined.
bRequirements were judged based on currently available experimental data. Note that the results for specific mutations may vary depending on nef alleles used and the nature of the mutated residues.
cThe requirement for the various motifs in Nef for pathogenesis was based on experiments with HIV-1 in the SCID/hu mouse model.
dDeduced from in vivo experiments with SIV. Note that the relative contributions of conserved motifs may differ between Nef proteins from HIV-1 and SIV.