HIV-1 replicates and persists in vaginal epithelial dendritic cells
Victor Pena-Cruz, Luis M. Agosto, Hisashi Akiyama, Alex Olson, Yvetane Moreau, Jean-Robert Larrieux, Andrew Henderson, Suryaram Gummuluru, Manish Sagar
Victor Pena-Cruz, Luis M. Agosto, Hisashi Akiyama, Alex Olson, Yvetane Moreau, Jean-Robert Larrieux, Andrew Henderson, Suryaram Gummuluru, Manish Sagar
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Concise Communication AIDS/HIV Infectious disease

HIV-1 replicates and persists in vaginal epithelial dendritic cells

Abstract

HIV-1 acquisition occurs most commonly after sexual contact. To establish infection, HIV-1 must infect cells that support high-level replication, namely CD4+ T cells, which are absent from the outermost genital epithelium. Dendritic cells (DCs), present in mucosal epithelia, potentially facilitate HIV-1 acquisition. We show that vaginal epithelial DCs, termed CD1a+ VEDCs, are unlike other blood- and tissue-derived DCs because they express langerin but not DC-SIGN, and unlike skin-based langerin+ DC subset Langerhans cells (LCs), they do not harbor Birbeck granules. Individuals primarily acquire HIV-1 that utilizes the CCR5 receptor (termed either R5 or R5X4) during heterosexual transmission, and the mechanism for the block against variants that only use the CXCR4 receptor (classified as X4) remains unclear. We show that X4 as compared with R5 HIV-1 shows limited to no replication in CD1a+ VEDCs. This differential replication occurs after fusion, suggesting that receptor usage influences postentry steps in the virus life cycle. Furthermore, CD1a+ VEDCs isolated from HIV-1–infected virologically suppressed women harbor HIV-1 DNA. Thus, CD1a+ VEDCs are potentially infected early during heterosexual transmission and also retain virus during treatment. Understanding the interplay between HIV-1 and CD1a+ VEDCs is important for future prevention and cure strategies.

Authors

Victor Pena-Cruz, Luis M. Agosto, Hisashi Akiyama, Alex Olson, Yvetane Moreau, Jean-Robert Larrieux, Andrew Henderson, Suryaram Gummuluru, Manish Sagar

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Figure 1

Vaginal CD1a+ cells are a unique DC subset.

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Vaginal CD1a+ cells are a unique DC subset. (A–E) Representative dot plo...
(A–E) Representative dot plots from a minimum of 3 independent donors show staining for CD1a along with (A) Langerin (CD207) , (B) DC-SIGN (CD209), (C) CD4, (D) CCR5, and (E) CXCR4. Numbers in the quadrants show the percentage of positive cells. Due to limited cell quantities, the CD1a+ VEDCs in these plots are not all from the same tissue. (F and G) Electron micrograph (EM) of the skin with markers denoting epithelium (E), Langerhans cell (LC), and dermis (D). The arrows point at morphological structures consistent with Birbeck granules (BG). (H and I) EM of vaginal tissue demonstrating epithelium (E) and a nucleated cell consistent with an epithelial-based dendritic cell (eDC). (J and K) EM of CD1a+ VEDC pellets with asterisks showing the CD1a beads. (L and M) Two independent Western blots of cell pellets from different vaginal tissue and skin donors. The vaginal epithelial (VE), vaginal CD1a+ cells (V CD1a), skin epithelial (SK), and skin Langerhans cells (SLC) were probed with Lag antibody (Takara), which is deemed specific for BGs. Expected band for BG binding is at 43 kDa, shown by arrow. Bottom blot shows probing for beta-actin.