BCA2/RABRING7 Interferes with HIV-1 Proviral Transcription by Enhancing the SUMOylation of IκBα

Marta Colomer-Lluch, Ruth Serra Moreno

Research output: Contribution to journalArticlepeer-review

Abstract

BCA2/Rabring7 is a BST2 co-factor that promotes the lysosomal degradation of trapped HIV-1 virions, but also functions as a BST2-independent anti-HIV factor by targeting Gag for lysosomal degradation. Since many antiviral factors regulate the NF-κB innate signaling pathway, we investigated whether BCA2 is also connected to this pro-inflammatory cascade. Here we show for the first time that BCA2 is induced by NF-κB-activating pro-inflammatory cytokines, and that up-regulation of BCA2 provides a regulatory negative feedback on NF-κB. Specifically, BCA2 serves as an E3 SUMO-ligase in the SUMOylation of IκBα, which in turn enhances the sequestration of NF-κB components in the cytoplasm. Since HIV-1 utilizes NF-κB to promote proviral transcription, the BCA2-mediated inhibition of NF-κB significantly decreases the transcriptional activity of HIV-1 (up to 3.7-fold in CD4+ T cells). Although the BCA2-induced block on NF-κB causes an overall 4-fold reduction in virus replication, HIV-1 partial
Original languageEnglish
JournalJournal of Virology
StatePublished - Apr 15 2017

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