Modeling Mucosal Cell-Associated HIV Type 1 Transmission in Vitro

Human immunodeficiency virus type 1 (HIV-1) can efficiently spread by direct cell-to-cell contact, a mechanism termed cell-associated HIV transmission. By some estimates, cell-associated HIV transmission is 10-1000-fold more effective than cell-free HIV infection. Mucosal cell-associated HIV transmission may occur when HIV-bearing cells in mucosal secretions from an HIV-infected donor transfer virus directly to recipient target cells in or below the mucosal epithelium, or through HIV transcytosis across the mucosal epithelium of a noninfected host. This mechanism may play an important role in the sexual and vertical transmission of HIV-1, yet most in vitro tests of vaccine and microbicide efficacy assess cell-free virus transmission. This article reviews in vitro assays that have been used to model mucosal cell-associated transmission, including microscopy, immune cell cocultures, use of HIV-infected cells in epithelial cell transcytosis assays, and cell-associated infection of mucosal tissue explants. Assays that authentically simulate mucosal cell-associated HIV transmission could provide valuable insight into mechanisms and molecules that can potentially be targeted for HIV prevention, as well as critical models for testing novel HIV prevention strategies for efficacy against cell-associated HIV transmission.