Modulation of HIV Binding to Epithelial Cells and HIV Transfer from Immature Dendritic Cells to CD4 T Lymphocytes by Human Lactoferrin and its Major Exposed LF-33 Peptide

Lactoferrin (LF), a multifunctional molecule present in human secretions, has potent inhibitory activities against human immunodeficiency virus (HIV). The aim of the study was to evaluate whether human LF (hLF) and its exposed domain LF-33 represented by the peptide (LF-33-GRRRRSVQWCAVSQPEATKCFQWQRNMRKVRGP) involved in LF-HIV gag binding and endotoxines neutralization, may inhibit early steps of HIV mucosal transmission. Human LF and the peptide LF-33 inhibited the attachment of primary X4-tropic HIV-1(NDK) and R5-tropic HIV-1(JR-CSF) strains to human endometrial (HEC-1) and colorectal (HT-29) CD4-negative epithelial cells, the purified hLF being more potent (up to 80%) than the LF-33 peptide. In addition, the hLF, but not the LF-33 peptide, inhibited up to 40% the transfer in trans of HIV-1(JR-CSF) and HIV-1(NDK,) from immature dendritic cells to CD4 T lymphocytes, likely in a DC-SIGN-dependent manner. Altogether, these findings demonstrate that hLF can interfere with HIV-1 mucosal transmission by blocking virus attachment to epithelial cells and by inhibiting virus transfer from dendritic cells to CD4 T cells, two crucial steps of HIV dissemination from mucosae to lymphoid tissue.