Human immunodeficiency virus-1 acquisition in genital mucosa: Langerhans cells as key-players.

Human immunodeficiency virus-1 (HIV-1) infection occurs primarily via genital mucosal tissues and the cellular mechanisms that affect HIV-1 acquisition are largely unclear. Langerhans cells (LCs) are professional antigen presenting cells lining the mucosal stratified squamous epithelium. It is becoming evident that LCs have different functions in HIV-1 transmission. HIV-1 can infect mucosal LCs, which subsequently efficiently transmit the virus to T cells in the lymphoid tissues. However, this seems to be dependent on the activation status of LCs, as immature LCs prevent HIV-1 infection by clearing invading HIV-1 though the C-type lectin langerin. Recent data demonstrate that co-infections with sexual transmitted infection (STIs) negate the protective function of LCs by different mechanisms, thereby allowing LC infection with HIV-1 and subsequently HIV-1 transmission. Here, we will discuss the function of LCs under normal circumstances and in the presence of STIs or inflammation. A better understanding of LCs function during homeostasis and inflammation is necessary for the development of new strategies to prevent HIV-1 infection.

Branched oligosaccharide structures on HBV prevent interaction with both DC-SIGN and L-SIGN.

Hepatitis B virus (HBV) is a DNA virus that infects the liver as primary target. Currently, a high affinity receptor for HBV is still unknown. The dendritic cell specific C-type lectin DC-SIGN is involved in pathogen recognition through mannose and fucose containing carbohydrates leading to the induction of an anti-viral immune response. Many glycosylated viruses subvert this immune surveillance function and exploit DC-SIGN as a port of entry and for trans-infection of target cells. The glycosylation pattern on HBV surface antigens (HBsAg) together with the tissue distribution of HBV would allow interaction between HBV and DC-SIGN and its liver-expressed homologue L-SIGN. Therefore, a detailed study to investigate the binding of HBV to DC-SIGN and L-SIGN was performed. For HCV, both DC-SIGN and L-SIGN are known to bind envelope glycoproteins E1 and E2. Soluble DC-SIGN and L-SIGN specifically bound HCV virus-like particles, but no interaction with either HBsAg or HepG2.2.15-derived HBV was detected. Also, neither DC-SIGN nor L-SIGN transfected Raji cells bound HBsAg. In contrast, highly mannosylated HBV, obtained by treating HBV producing HepG2.2.15 cells with the alpha-mannosidase I inhibitor kifunensine, is recognized by DC-SIGN. The alpha-mannosidase I trimming of N-linked oligosaccharide structures thus prevents recognition by DC-SIGN. On the basis of these findings, it is tempting to speculate that HBV exploits mannose trimming as a way to escape recognition by DC-SIGN and thereby subvert a possible immune activation response.