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

• Published in: Viruses 2021-11, Vol.13 (11), p.2266
• Main Authors: Gokavi, Jyotsna, Sadawarte, Sharwari, Shelke, Anant, Kulkarni-Kale, Urmila, Thakar, Madhuri, Saxena, Vandana
• Format: Article
• Language: English
• Subjects: Antiviral Restriction Factors - genetics; Cell Line; cervical; Cervix Uteri - cytology; Cervix Uteri - metabolism; Cervix Uteri - virology; Communication; Cytokines; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - virology; Female; Gene expression; HIV; HIV-1 - physiology; host restriction factors; Human immunodeficiency virus; Humans; Infections; Latency; Lymphocytes; microRNA; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; miR-155; miRNA; Mucosa; Reagents; Signal Transduction - genetics; TGF-β; Transforming Growth Factor beta - antagonists & inhibitors; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Virus Shedding
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13112266

TGF-β 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-β 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-β plays an important role as a negative regulator of HIV release in the infected cervical epithelial cells. Inhibition of miR-155 upregulated TGF-β signaling and mRNA expression of host restriction factors such as , and , while decreased the HIV release in ME-180 cells. To conclude, this is the first study to decipher the complex interplay between TGF-β, miR-155 and HIV release in the cervical epithelial cells. Collectively, our data suggest the plausible role of TGF-β in promoting HIV latency in cervical epithelial cells which needs further investigations.