HIV TYPE 1 FAILS TO TRIGGER INNATE IMMUNE FACTOR SYNTHESIS IN DIFFERENTIATED ORAL EPITHELIUM.
This study by scientists at Prince of Songkla University (Thailand), the University of Washington, Fred Hutchinson Cancer Research Center and MatTek Corp. demonstrated that MatTek’s EpiOral in vitro 3-D human buccal (inner cheek) tissue equivalent can be used to model the in vivo response to HIV-1 virus exposure. The oral mucosa is relatively resistant to human immunodeficiency virus type 1 (HIV-1) transmission. The mechanisms contributing to this resistance remain incompletely understood, but may include HIV-induced synthesis of innate immune factors. Researchers used fully differentiated oral epithelium (EpiOral) as a surrogate for the oral mucosa in vivo, exposed it to X4- and R5-tropic HIV-1 in culture, and quantified mRNA expression of six innate immune factors. Neither virus increased expression of human beta defensin 2 (hBD-2) mRNA over supernatants from uninfected lymphoblast controls. HIV-1 also failed to induce mRNA of four additional innate immunity-related genes. Similar results were obtained with oral monolayer epithelial cells. Interestingly, the X4-tropic virus inhibited mRNA expression of hBD-2, and of three of the other factors, at higher dosages in the differentiated oral epithelium, but not the monolayers. The failure of HIV-1 to induce innate immune factors in the differentiated epithelium was not due to a lack of tissue penetration, as we detected fluorescence-tagged virions up to 30 µm deep from the apical surface. HIV-1 does not trigger de novo innate immune factor synthesis in oral epithelium, pointing to the role of a constitutive innate immunity for protection against HIV-1 in the oral cavity.
CCL5, Chemokine (C-C motif) ligand , Confocal microscopy, EpiOral, HIV, HIV-1, HIV-1 binding, HIV-1 penetration, Human beta defensin 2 (hBD-2), IL-1beta, IRF1, Innate immune factor, Interferon regulatory transcription factor, Interleukin-1beta, Mock-infected PHA-stimulated lymphoblasts, ORL-200, Oral mucosa, R5-tropic HIV-1, SLPI, Secretory leukocyte protease inhibitor, X4-tropic HIV-1
HIV, R5-tropic HIV-1, TNF-alpha, X4-tropic virus
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