Pustaka Ilmiah Universitas Padjadjaran

Abstrak

HIV-ASSOCIATED DISRUPTION OF TIGHT AND ADHERENSJUNCTIONS OF ORAL EPITHELIAL CELLS FACILITATES HSV-1INFECTION AND SPREAD

Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In theseimmunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such asulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-inducedimmune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this reportwe show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelialcells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinasesignaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between theepithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesionprotein and critical receptor for HSV envelope glycoprotein D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD,which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intactjunctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infectedto uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cellspread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIVexposednectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possiblemechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.