We next investigated the impact of the HIV-1 associated promoter variants on both DC-SIGN transcriptional activity in vitro and expression in fetal macrophages (Hofbauer cells). Variant p-336C decreased the transcriptional activity of Sp1 binding site [25, 31] . Transcription factor binding site analysis predicted that variant p-201A would create a c-myc binding site. To test the effect of these promoter variants on transcription, we transiently transfected HeLa cells with a luciferase reporter gene under the control of DC-SIGN promoter region -507 to -1 containing AP-1, Sp1, Ets-1 and NF-KB transcription factors that are essential for promoter activity [32] and harbouring promoter WT p-336T/p-201C or variant p-336C/p-201A sequences ( Figure 2A ). As previously reported [25, 31] , the luciferase activity of the p-336C/p-201C variant construct was lower than that of WT p-336T/p-201C ( Figure 2B ) but the decreased did not reach significance in our assay. The p-201A variant either alone or in combination with p-336C significantly reduced DC-SIGN transcriptional activity in vitro (Ratio p-336T/p-201C/p-336C/p-201A = 3.13, P = 0.0039). Uninfected infants harboured more frequently H1 and H2 haplotypes reaching significance for H2 (Table 1) . H2 carries two promoter variants, p-939T and p-139C, that differ from WT H1 haplotype ( Figure 1B) . The promoter variants p-939T and p-139C did not show any influence on DC-SIGN transcriptional activity in vitro ( Figure S1 ).