Abstract
Emtricitabine (FTC) is an antiviral medication designed to diminish the presence of HIV in the body, thereby impeding or preventing harm to the immune system and the onset of AIDS-related illnesses. The precise mechanisms underlying emtricitabine's inhibition of HIV-1 replication in pre-exposure prophylaxis (PrEP) are not fully comprehended. This investigation delves into the impact of emtricitabine treatments in vitro, utilizing the susceptible Jurkat cell line. Employing a sensitive real-time PCR assay and Western blotting analysis, we observed that emtricitabine pre-treatment effectively impedes HIV-1 replication. Additionally, when the treatment is discontinued, viral replication is reactivated through the recruitment of host transcription factors, such as NF-κB p65, NFAT, Ap-1, and Sp-1. Both pre-treatment and post-treatment with emtricitabine demonstrated the ability to reduce HIV production through various cellular signaling pathways. These include the attenuation of TCR-related, PI3K, and MAPK-mediated pathways, the downregulation of p-TEFb pathways responsible for transcription elongation, the obstruction of TLR signaling pathways affecting the host immune response, and the inhibition of Jak-Stat pathways associated with viral enhancement. Discontinuation of emtricitabine treatments reactivated HIV-1 replication by upregulating these cellular signaling pathways. The data strongly suggest that long-term PrEP offers continuous protection against HIV, presenting itself as a viable option for individuals consistently at high risk of infection. This ensures a steadfast and dependable form of protection.
Keywords
HIV-1, Replication, ART, PrEP, Emtricitabine, Latency, TCR