CCAAT Enhancer Binding Protein and Nuclear Factor of Activated T Cells Regulate HIV-1 LTR via a Novel Conserved Downstream Site in Cells of the Monocyte-Macrophage Lineage
Figure 1
Physical position and consensus sequence comparison of DS3 among HIV-1 subtypes A, B, C, and D and differential binding phenotype in CXCR4 and CCR5-utilizing viruses.
(A) Genbank and LANL were searched for HIV-1 LTR sequences from subtypes A, B, C, and D resulting in 7,577 sequences. The MUSCLE alignment tool and TRANSFAC software were used to identify a predicted binding site for C/EBP factors from+158 to+172 with respect to the start site. This region was then used to construct a new consensus binding sequence for each of the four predominant subtypes in the dataset. (B) Comparison of nucleotide sequence deviations, from the consensus subtype B configuration, in important transcription factor binding sites in the LTR both upstream and downstream of the start site. (C) Sequence logos generated from 1,832 sequences which contained both LTR and envelope V3 sequence grouped by CXCR4 and CCR5 coreceptor utiliziation using WebPSSM. The differences observed were not statistically significant (Fischer’s exact test). (D) Survival function (1 - cdf) of the distribution of Jaspar binding scores for the NFAT and CEBP sites of the DS3 region for sequences in C grouped by predicted coreceptor utilization. The vertical black bars represent the binding threshold with a false positive rate of 0.01.