Inhibition of miR-155 Promotes TGF-beta Mediated Suppression of HIV Release in the Cervical Epithelial Cells

TGF-beta has been shown to play a differential role in either restricting or aiding HIV infection in different cell types, however its role in the cervical cells is hitherto undefined. Among females, more than 80% of infections occur through heterosexual contact where cervicovaginal mucosa plays a critical role, however the early events during the establishment of infection at female genital mucosa are poorly understood. We earlier showed that increased TGF-beta level has been associated with cervical viral shedding in the HIV infected women, however a causal relationship could not be examined. Therefore, here we first established an in vitro cell-associated model of HIV infection in the cervical epithelial cells (ME-180) and demonstrated that TGF-beta plays an important role as a negative regulator of HIV release in the infected cervical epithelial cells. Inhibition of miR-155 upregulated TGF-beta signaling and mRNA expression of host restriction factors such as APOBEC-3G, IFI-16 and IFITM-3, while decreased the HIV release in ME-180 cells. To conclude, this is the first study to decipher the complex interplay between TGF-beta, miR-155 and HIV release in the cervical epithelial cells. Collectively, our data suggest the plausible role of TGF-beta in promoting HIV latency in cervical epithelial cells which needs further investigations.