HIV-1 Tat-mediated microglial inflammation involves a novel miRNA-34a-NLRC5-NF κB signaling axis.

HIV-1 Tat-mediated microglial inflammation involves a novel miRNA-34a-NLRC5-NFκB signaling axis.
Brain Behav Immun. 2019 Mar 11;:
Authors: Periyasamy P, Thangaraj A, Bendi VS, Buch S
Abstract
While the advent of combination antiretroviral therapy (cART) has dramatically increased the lifespan of people living with HIV-1 paradoxically, the prevalence of NeuroHIV in people treated with cART is on the rise. It has been well documented that despite the effectiveness of cART in suppressing viremia, CNS continues to harbor viral reservoirs with persistent low-level virus replication. This, in turn, leads to the presence and accumulation of early viral protein - HIV-1 Tat, that is a well-established cytotoxic agent. In the current study, we demonstrated that exposure of mouse microglia to HIV-1 Tat resulted both in a dose- and time-dependent upregulation of miRNA-34a, with concomitant downregulation of NLRC5 (a negative regulator of NFκB signaling) expression. Using bioinformatics analyses and Argonaute immunoprecipitation assay NLRC5 was identified as a novel target of miRNA-34a. Transfection of mouse primary microglia with miRNA-34a mimic significantly downregulated NLRC5 expression, resulting in increased expression of NFκB p65. In contrast, transfection of cells with miRNA-34a inhibitor upregulated NLRC5 levels. Using pharmacological approaches, our findings showed that HIV-1 Tat-mediated microglial activation involved miRNA-34a-medi...

Source: Brain, Behavior, and Immunity - March 10, 2019 Category: Neurology Authors: Periyasamy P, Thangaraj A, Bendi VS, Buch S Tags: Brain Behav Immun Source Type: research