Novel Anti-Retroviral Drug Targets: Interfering siRNA and MitochondrialTERT Expression

Abstract

Telomerase can be touted as the miracle anti-aging enzyme that reverses the age-related attrition of telomere ends. The catalytic subunit of telomerase, TERT telomerase reverse transcriptase, is known to function as an RNA dependent DNA polymerase in the nucleus (TERT-TERC), as an RNA dependent RNA polymerase, an RdRP (TERT-RMRP), in mitochondria, and, as TERT alone interacting with master regulators for cell and organellar protection to promote global survival and rejuvenation potential. TERT shows conservation of the viral polymerase structure, and like viral polymerases, is capable of producing cDNA, double stranded RNA, and like HIV reverse transcriptase, is inhibited by some HIV reverse transcriptase inhibitors. TERT also shows promiscuous partnering with RNA elements, RMPR, tRNA, and TERC. TERT, with its versatile viral-like functions, seems like a valuable hostage for viral infection. Telomerase is inhibited by viral proteins. When the role of telomerase in HIV infection is reviewed, telomerase modulation emerges as a valuable player in HIV therapy intervention. Induced viral protein and some reverse transcriptase HIV drugs promote TERT deficit which might be counteracted by TERT up regulation, or preference for use of drugs that do not target host reverse transcriptase, in order to preserve the health promotion of TERT pathways especially mitochondrial protection against oxidative stress, and inhibition of pathways that promote immune deficiency. Telomerase “dark side” dysfunctional overexpression might be targeted using an anti-cancer-like vaccine, delivered selectively to viral reservoirs. The use of siRNA’s to inactivate proteins that promote viral survival offer promising potential success in anti-retroviral therapy, with the ability to block mico RNAs favorable for viral progression. Strategies and therapy that interfere with the HIV-TAR interaction offer the desirable ability to stop infection before it starts. Mimetics of exercise, hibernation, anti-aging supplements, and mitochondrial targeted antioxidants offer antiviral potential and disease vulnerability from fallout of immune deficiency.