Background: DC-SIGNR and DC-SIGN may bind HIV-1 and mediate efficient infection of CD4⁺ T-lymphocytes in trans. It was reported that alternative splicing of DC-SIGNR and DC-SIGN pre-mRNA generated a wide repertoire of transcripts encoding membrane associated and soluble isoforms. Total of 9 DC-SIGNR transcript isoforms were identified from placenta and liver. Inter-individual variation in the repertoire of DC-SIGNR transcript expression was also reported in placenta, which might play a role in parental transmission of HIV-1. However, the DC-SIGNR transcripts in dendritic cells (DCs) and mucosa, which may involve in sexual transmission of HIV-1, have not been characterized.

Methods: DCs (n = 4) were cultured from monocytes in the presence of IL-4 and GM-CSF, and total RNA was extracted on day 7. Total RNA was also isolated from rectum biopsies (n = 2) that were submerged immediately in the RNA stabilization reagent and keep at -20°C. Full length DC-SIGNR genes from monocyte derived DCs and rectum biopsies were amplified by RT-PCR, cloned, and sequenced.

Results: Both membrane associated form (Fig. 1) and soluble form (Fig. 2) of DC-SIGNR are detected in human DCs and rectum biopsies. Only the prototypes of the 2 forms are shown in Figs. 1 and 2. There is also extensive inter-individual heterogeneity in the transcript repertoire. We found total of 20 distinct transcripts, of which 14 were seen only in DCs, 2 only in rectum biopsies and 4 in both. The 18 transcript isoforms we newly identified contain deletion of up to 5 repeats in the repeat region, deletion of exon II, deletion of exon III, deletion of exon VI, deletion of the last 69 bp of exon IV, deletion of part of exon II, and retaining intron I and part of intron VI.

Conclusions: We found a large repertoire and wide inter-individual heterogeneity of DC-SIGNR transcript isoforms from human DCs and rectum biopsies. These variations could play a role in sexual transmission of HIV-1.