In addition to the enhancement of HIV-1 capture and transmission to target cells, DC-SIGN genetic variants may also contribute to a local immunological environment that promotes viral replication and dissemination of HIV-1 across the placenta [17, 19] . HIV-1 or HIV-1-derived products activated fetal macrophages and T lymphocytes and promoted the establishment of a productive infection within the placenta [46, [48] [49] [50] . In response to dengue infection, MDCCs from DC-SIGN p-336CT heterozygous individuals produced higher levels of pro-inflammatory factors such as TNF-alpha, IL-12 and IP-10 than those from WT p-336TT homozygotes [51] . Moreover, TNF-alpha enhanced HIV-1 replication and transcytosis within the placenta and TNFalpha level correlated with the amount of HIV-1 transcripts [52] [53] [54] . It is tempting to speculate that infants harbouring the p-336TT genotype, such as H1 and H2 carriers, may produce less TNF-alpha to reduce or thwart HIV-1 replication in the placenta.