HIV TYPE 1 FAILS TO TRIGGER INNATE IMMUNE FACTOR SYNTHESIS IN DIFFERENTIATED ORAL EPITHELIUM.

• TR Number: 551
• Keywords: 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

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.