Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans -Infection of CD4 ⁺ T Cells

Abstract

Despite great advances in antiretroviral therapies, human immunodeficiency virus type 1 (HIV-1) infection still remains a major global epidemic. Sexual transmission is the principal route of HIV-1 acquisition, making the genital and rectal mucosae the major sites of viral transmission. The intestinal mucosa is also the primary site where HIV-1 amplifies to disseminate virus throughout the host and is critical in the early events in the establishment of infection and evasion of immune defenses. However, the mechanisms contributing to the establishment of HIV-1 primary infection remain largely unexplored. Cell-associated viral dissemination has been proposed to play pivotal roles in HIV-1 primary infection, and multiple cell types, such as dendritic cells (DCs) and macrophages, have been reported to be hijacked by HIV-1 for local and systemic viral spread (1-4). DCs provide one of the best-described cell models for understanding cell-mediated HIV-1 capture and dissemination (1,(5)(6)(7)(8).Mast cells are derived from hematopoietic progenitor cells and undergo final maturation in vascularized tissues. Mast cells are strategically in close contact with the host-environment interface, such as the skin, airway, gastrointestinal tract, and urinary tract. They express numerous pathogen-associated molecular patterns and play an important role in the early immunosurveillance for many pathogens (9, 10). Mast cells can interact with various immune cells in complex ways, including release of soluble factors and direct contact (11), and are important immune effector and modulatory cells that help to link innate and adaptive immunity in the fight against pathogens (9,(12)(13)(14). They have been shown to be important for host defense against various viruses, such as vesicular stomatitis virus, Sendai virus, hantavirus, reovirus, dengue virus, influenza virus, herpes simplex virus, and murine cytomegalovirus (15-23). Additionally, mast cells can serve as antigenpresenting cells and participate in traditional immunologic synapse formation with T cells to mediate antigen-specific T cell activation (24).

Are Basophils and Mast Cells Masters in HIV Infection?

“…Using confocal microscopy, they found that contact between basophils and CD4 + T cells is required for viral transfer. More recently, the same group extended the previous observations showing that also human intestinal mast cells can capture HIV and mediate viral trans- infection of CD4 + T cells [74]. Collectively, these fascinating results suggest that direct contact between basophils/mast cells and CD4 + T cells and the formation of infection synapses facilitate trans- infection of HIV particles.…”

“…By contrast, there is no evidence that human basophils can be infected by HIV [73]. However, recent evidence suggests that human basophils and mast cells can capture HIV and can mediate viral trans- infection of CD4 + T cells [73,74]. A strategy designed to prevent basophil/mast cell-mediated viral capture and transfer may represent a novel direction for the development of anti-HIV treatment.…”

HIV-1 gp120 Glycoprotein Interacting with Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Down-Regulates Tight Junction Proteins to Disrupt the Blood Retinal Barrier and Increase Its Permeability

“…HIV-1 Viral Stocks-HIV virus-like particles (VLPs) were generated by co-transfecting HEK293T cells with or without a plasmid containing Gag-GFP and plasmids expressing JRFL or HXB2 HIV envelope proteins, respectively (44,55). Cell-free supernatant was harvested, filtered, and titrated using a p24 gag capture ELISA.…”

Endoplasmic Reticulum Protein SCAP Inhibits Dengue Virus NS2B3 Protease by Suppressing Its K27-Linked Polyubiquitylation

“…The cells were maintained in a humidified 5% CO 2 incubator at 37°C. Human monocyte-derived DCs were prepared as described previously (43,44).…”