Background: DC-SIGN and DC-SIGNR efficiently bind and transmit HIV-1 to susceptible cells in trans. Both DC-SIGN and DC-SIGNR are organized into 3 domains: an N-terminal cytoplasmic region, a neck region containing 7 repeats of the 23 amino acid sequence, and a C-terminal domain with homology to C-type lectins. DC-SIGNR repeat region is highly polymorphic. However, the effect of DC-SIGNR repeat region polymorphisms on HIV-1 transmission and disease progression is not known.

Methods: The studied cohorts include 59 exposed seronegative (ES) who have had repeated, unprotected sexual contacts with HIV-1 infected partners, 361 HIV-1 negatives, and 232 HIV-1 positives including 19 long-term non-progressors (LTNP). The DC-SIGNR repeat region was amplified from genomic DNA extracted from PBMC, and alleles were distinguished by 3% agarose gel electrophoresis. Cloning and sequencing were used to get the sequence from allele 3 to 9. Fisher’s exact test was used for statistic analysis.

Results: We found 15 genotypes in the DC-SIGNR repeat region based on numbers of repeats (ranging from 3 to 9). The allele frequencies found in all studied populations were 1.6% for allele 9, 0.2% for allele 8, 53.7 % for allele 7, 14.9% for allele 6, 26.6% for allele 5, 2.9% for allele 4, and 0.1% for allele 3. The frequency of homozygous 7/7 was lower in ES (11.9%) than in HIV-1 infected (30.2%, p = 0.004) or in HIV-1 negative individuals (32.1%, p = 0.001), whereas heterozygous 7/5 was higher in ES (42.4%) than in HIV-1-infected (22.8%, p = 0.004) or in HIV-1 negative individuals (7/5 26.9%, p = 0.019). Homozygous 5/5 tended to be more prevalent among ES (15.3%) than in HIV-1-infected (8.6%, p = 0.145) or in HIV-1 negative individuals (7.2%, p = 0.070). The frequency of allele 5 was higher in ES (42.4%) than in either HIV-1-infected (25.7%, p = 0.0006) or HIV-1 negative individuals (24.5%, p = 0.0001), whereas allele 7 tended to be less common in ES (40.7%) than in HIV-1 infected (51.9%, p = 0.031) or HIV-1 negative individuals (56.9%, p = 0.001).

Conclusions: The homozygous DC-SIGNR 7/7 repeat is associated with an increased probability of HIV-1 transmission, whereas the heterozygous 7/5 or homozygous 5/5 correlates with resistance to HIV-1 infection. The allele 5 may act as a resistance factor, while the allele 7 may serve as a risk factor for acquiring HIV-1.