Expression levels of the innate response gene RIG-I and its regulators RNF125 and TRIM25 in HIV-1 infected adult and pediatric individuals

Abstract

Objective: TLRs (toll-like receptors) and RLRs (RIG-I-like receptors) mediate innate immune responses by detecting microorganism invasion. RIG-I activation results in the production of interferon (IFN) type 1 and IFN responsive genes (ISGs). Since the ubiquitin ligases RNF125 and TRIM25 are involved in regulating RIG-I function, our aim was to assess whether the levels of these three genes vary between healthy and HIVinfected individuals and if these levels are related to disease progression. Design: Gene expression analysis for RIG-I, RNF125 and TRIM25 were performed for HIV infected adults and children?s PBMCs. Methods: RT-qPCRs were performed in order to quantify the expression levels of RIG-I, RNF125 and TRIM 25 from control or HIV infected individuals isolated PBMCs. Results: Controls express higher levels of the three genes when compared to HIVinfected patients. These expressions are clearly distinct between healthy and progressors, and are reproduced in adults and children. In controls, RNF125 is the highest expressed gene while in progressors, RIG-I is either the highest expressed gene or is expressed similarly to RNF125 and TRIM25. Conclusions: A pattern of expression of RIG-I, RNF125 and TRIM25 genes in HIV patients is evident. The high expression of RNF125 in healthy individuals reflects the importance of keeping RIG-I function off, inhibiting unnecessary IFN production. Consistent with this assumption, RNF125 levels are lower in HIV patients and importantly, the RNF125/RIG-I ratio is lower in patients that progress to AIDS. Our results might help to predict disease progression and unveil the role of poorly characterized host genes during HIV infection.