HIV-1 infection in the female reproductive tract: role of interactions between HIV-1 and genital epithelial cells

Abstract

Despite recent progress in understanding the mucosal transmission of human immunodeficiency virus (HIV)-1, the immediate events following transmission in the female genital tract are incompletely understood. Recent in vivo studies in primate models indicate that HIV-1 transmission may occur in the upper or lower genital tract and the initial HIV-1 replication occurs primarily in the target T cells and in some subsets of DCs localized in the genital tract. However, the principal mechanism(s) that allow the virus to cross the primary barrier of genital epithelial cells (GECs) are still unclear. A number of pathways have been proposed as possible ways that HIV-1 could use to cross the epithelium. However, little attention has been paid to the response of GECs to HIV-1. We recently demonstrated that exposure to HIV-1 rapidly upregulates a wide array of pro-inflammatory cytokine production by GECs. Among these cytokines, tumour necrosis factor (TNF)-α impaired the tight junction barrier allowing HIV-1 and luminal bacteria to translocate across the epithelium. This study illustrated that GECs are dynamically active cells that mount rapid host responses to HIV-1, independent of viral replication. Cytokine responses of GECs could play a critical role in HIV transmission and replication. Further understanding of GEC responses to HIV-1 and their regulation could be critical to understanding HIV-1 transmission dynamics during heterosexual transmission.