The HIV-1 Transcriptional Repressor TRIM22 Is a Novel Determinant of Proviral Latency and Disease Progression

Filippo Turrini

Host restriction factors contribute to contain HIV-1 infection and replication. Among them, we have previously characterized the TRIpartite Motif-containing protein 22 (T22) as inhibitor of either basal or induced HIV-1 proviral transcription. In the first part of this project we started to dissect the molecular mechanism of T22 restriction and demonstrated that it curtails acute HIV-1 replication by preventing the binding of the cellular transcription factor (TF) Sp1 to the viral promoter. We have next evaluated if T22 could also play a role in chronically infected T-cell lines J-Lat 10.6 and ACH-2 characterized by a constitutive state of proviral latency reversible upon cell stimulation with latency reversing agents (LRA). Indeed, we have observed that shRNA-mediated silencing of T22 expression in these cells leads to reversal of latency both in unstimulated conditions (ACH2) and upon LRA-stimulation (both cell lines).
In addition, to these in vitro studies, we have recently identified a loss-of-function T22 allelic variant lacking the HIV-1 restriction activity, which is overrepresented in a cohort of patients in advanced HIV-1 disease stage. Furthermore, by comparing the 1000 Genomes Project database, we have identified two additional allelic variants that define two separate groups of distinct haplotypes. As these variants are quantitative trait loci (eQTL) that contribute to T22 mRNA expression, they might have a potential role in T22 antiviral activity.

Anna Scotti
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