BCA2/Rabring7 interferes with HIV-1 proviral transcription by enhancing the SUMOylation of IκBα

Marta Colomer-Lluch, Ruth Serra-Moreno

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

BCA2/Rabring7 is a BST2 cofactor 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 proinflammatory cascade. Here, we show for the first time that BCA2 is induced by NF-κB-activating proinflammatory cytokines and that upregulation of BCA2 provides 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 4.4-fold in CD4+ T cells). Therefore, our findings indicate that BCA2 poses an additional barrier to HIV-1 infection: not only does BCA2 prevent assembly and release of nascent virions, it also significantly restricts HIV-1 transcription by inhibiting the NF-κB pathway.

Original languageEnglish
Article numbere02098-16
JournalJournal of Virology
Volume91
Issue number8
DOIs
StatePublished - Apr 1 2017

Keywords

  • Host-pathogen interactions
  • Human immunodeficiency virus
  • Innate immunity
  • NF-κB
  • Virology

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