TABLE 1.
MUT1 and MUT2 mutationsa
| Location | Nucleotide
mutation(s) |
Amino acid
change |
Found in | Comment(s) |
|---|---|---|---|---|
| 5′LTR/3′LTR/Nef | C200A/C9275A | Ser163Arg | MUT1/MUT2 | Nucleotide located at the 3′ extremity of the 5′ LTR nucleosome 0 binding site (67, 68). |
| Corresponds to the first nucleotide of a putative 5′ LTR C/EBP binding site (69, 70). |
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| Residues in the Nef dileucine motif ENTSLL known to interact with AP-2 protein and downregulate CD4 (55). |
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| G267A/G9342A | Asp186Asn | MUT2 | Mutation of a main Nef residue in the β-catenin binding motif D186-X-X-X-X-[F/Y191] (59). |
|
| T318G/T9393G | Phe203Val | MUT2 | Mutation of the first nucleotide of the consensus TCF-4/LEF-1 binding site TACAAAG, site of the TCF-4/β-catenin/SMAR1 complex known to repress HIV-1 transcription (71, 72). |
|
| Tyrosine motif Tyr202/[Phe/Tyr]203 in the C-terminal flexible loop of Nef is involved in CD4 receptor endocytosis (61). |
||||
| 5′LTR/3′LTR | 49-nt insertionb
downstream of nt 390 and 9465 |
MUT1 | Two NF-κB/one Sp1 insertion. | |
| G421A/G9496A | MUT2 | Upstream (position −4) of the TATA box. | ||
| C425T/C9500T | MUT1/MUT2 | Mutation of the HIV-1 TATA box CATATAA at position +1 to TATATAA known to slightly increase viral fitness (39). |
||
| T453G/T9598G | MUT1/MUT2 | Position −2 of the transcription start site (TSS) and at the basis of the TAR hairpin. |
||
| Gag | G1498A | Ala237Thr | MUT1/MUT2 | Found in the N-terminal domain of mature p24 capsid protein (73). |
| A1533G | Gly248 (silent) | MUT2 | ||
| Pol | G3166A | Arg361Lys | MUT2 | Found in the basic loop of the RNase H domain of the reverse transcriptase (74). |
| Vif | G5177A | Ser46Asn | MUT1/MUT2 | Residue part of the 45ESTN48 motif shown to play a role in CBF β interaction (75). |
| Vpr | G5730 deletion | C-terminal truncation resulting in Vpr1-57 plus LysPro in the C terminus |
MUT1/MUT2 | The Vpr truncation (aa 58 to 96) encompasses the third helix of Vpr (aa 56 to 77) and its flexible C-terminal region (76). |
| Tat | C5922T | Cys31 (silent) | MUT1 | |
| C5943T | Phe48 (silent) | MUT1/MUT2 | ||
| Env | G6719C | Asp167His | MUT1/MUT2 | Residue in the V2 loop of Env gp120. Epitope for neutralizing antibodies (77). |
a
Numbering is based on the pNL4-3 sequence (GenBank accession no. AF324493.2). Amino acid numbering is based on each individual viral protein. nt, nucleotides; aa, amino acids.
b
The 49 nucleotides inserted are TGCTACAAGG AACTTTCCGC TGGGGACTTT CCAGGGAGGC GTGGCCTGG.