Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction

• DOI: 10.1371/journal.ppat.1006247
• Publication Date: 2017-02-27T18:47:57Z
• Authors: Aizezi Yasen; Rossana Herrera; Kristina Rosbe; Kathy Lien; Sharof M. Tugizov
• Keywords: CD4-Positive T-Lymphocytes; Male; 0301 basic medicine; QH301-705.5; Mononuclear; Blotting, Western; Foreskin; Palatine Tonsil; Fluorescent Antibody Technique; HIV Infections; Cervix Uteri; 618; 03 medical and health sciences; 616; Leukocytes; Humans; Biology (General); Mucous Membrane; Blotting; Macrophages; Epithelial Cells; Dendritic Cells; RC581-607; Coculture Techniques; 3. Good health; HIV-1; Leukocytes, Mononuclear; Female; Immunologic diseases. Allergy; Transcytosis; Western; Research Article

Oropharyngeal mucosal epithelia of fetuses/neonates/infants and the genital adults play a critical role in HIV-1 mother-to-child transmission sexual virus, respectively. To study mechanisms through epithelium, we established polarized tonsil, cervical foreskin epithelial cells. Analysis cells showed that approximately 0.05% initially inoculated virions transmigrated via epithelium. More than 90% internalized were sequestered endosomes cells, including multivesicular bodies (MVBs) vacuoles. Intraepithelial remained infectious for 9 days without viral release. Release intraepithelial was induced by calcium ionophore ionomycin cytochalasin D, which increase intracellular disrupt cortical actin Cocultivation containing with activated peripheral blood mononuclear CD4+ T lymphocytes led to disruption spread virus from lymphocytes. Treatment proinflammatory cytokines tumor necrosis factor-alpha interferon gamma also reorganization release virus. Inhibition MVB formation small interfering RNA (siRNA)-mediated silencing its protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) expression reduced sequestration ~60-70%. Furthermore, inhibition vacuole siRNA-inactivated rabankyrin-5 significantly Interaction intercellular adhesion molecule-1 function-associated antigen-1 important inducing facilitating cell-to-cell This mechanism may serve as pathway transmission.