Transmission of Macrophage‐Tropic HIV‐1 by Breast‐Milk Macrophages via DC‐SIGN

Abstract

Recent findings suggest that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) produced in colostrum/early breast milk may hold a clue to determine the mechanisms of transmission of HIV-1 via breast-feeding. Here, we show that the majority of CD4(+) cells in the colostrum are CD14(+) macrophages expressing both chemokine receptors and DC-SIGN, a dendritic cell-specific receptor for HIV-1. The R5-type macrophage-tropic HIV-1 isolate NL(AD8) infected such breast-milk macrophages and caused them to secrete virus particles efficiently; however, the secreted virions showed only a weak transmissibility to their susceptible target, MAGIC-5 cells. When stimulated with interleukin-4, the breast-milk macrophages demonstrated a striking enhancement of expression of DC-SIGN and showed a strong capacity to transmit NL(AD8) virions to MAGIC-5 cells, which was specifically blocked by anti-DC-SIGN-specific antibody. These results suggest that HIV-1 virions captured by DC-SIGN, but not secreted cell-free virions, may be more efficiently transmitted to other compartments, such as the gastrointestinal tract, through acidic gastric juice.

Susceptibility of Human Testis to Human Immunodeficiency Virus-1 Infection in Situ and in Vitro

“…DC-SIGN expression by tissue resident macrophages has previously been described in the lung 46 and the placenta. 47 Recently, DC-SIGN was shown on perivascular macrophages within the central nervous system 48 and macrophages in breast milk, 49 further demonstrating that this receptor is not solely expressed by dendritic cells. Within the testicular interstitial tissue, we have also evidenced a dendritic cell population (CD68 ϩ S100 ϩ cells 50 ) that did not express DC-SIGN.…”

Comparison of Human Immunodeficiency Virus Type 1-Specific Inhibitory Activities in Saliva and Other Human Mucosal Fluids

“…We are aware that a significant proportion of HIV in these mucosal fluids occurs as infected leukocytes and that cell-associated virus may more effectively transmit HIV-1 than cell-free virus (14,40,42). However, our primary aim was to directly compare intrinsic anti-HIV-1 inhibitory activities in a variety of mucosal fluids and since mucosal secretions appear to inhibit cell-free virus more effectively than cell-associated virus (14,40,42), a cell-free assay system was utilized. Furthermore, we utilized the CXCR4-using, laboratory-adapted HIV-1 strain HIV-1 RF and transformed T cells.…”

Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

“…Our data are similar to those reported in cohorts of heterosexual transmission, where the likelihood of transmission of multiple variants is around 20%, and overall suggest that the low probability of transmission for any given exposure generally results in the transmission of a single variant when an infection does occur. 12,[28][29][30][31][32][33][34] We next compared the number of putative N-linked glycosylation sites (N-glycosite program, hiv.lanl.gov) and sequence length between mother and infant viral populations. Fewer glycosylation sites and shorter full-length env sequences were seen in infants compared to their mothers over env in all three transmission pairs (Supplementary Table S1).…”