Bile-salt stimulated lipase in human milk binds DC-SIGN and inhibits HIV-1 transmission

Background Approximately 20% of HIV-1 infected breastfeeding mothers transmit virus to their infants. It has been hypothesized that dendritic cells expressing C-type lectins, such as DC-SIGN, play an important role in the establishment of infection with HIV-1 and several other pathogens. Within our laboratory we have identified that Bile Salt Stimulated Lipase (BSSL) is able to bind to DC-SIGN and block HIV-1 transmission via dendritic cells. The C-terminal part of BSSL contains a highly polymorphic repeat section coded by exon 11 of the gene and is composed of an array of 11 amino acid repeats. Materials and methods We have studied a large number of human milk samples from HIV-1 negative mothers. The BSSL protein was analyzed by size fractionation and iso-electric focusing. We studied the genomic structure of the gene through PCR amplification and sequencing of the BSSL repeats for a group of selected mothers. Results Milk samples from a large number of different mothers (n=25) were identified that demonstrated variant levels of inhibition to viral transfer. We have studied specific BSSL genotypic as well as phenotypic properties in order to identify what provides for the large variation of milk binding DC-SIGN. The tested milk samples were divided into