TY - JOUR
T1 - BCA2/Rabring7 interferes with HIV-1 proviral transcription by enhancing the SUMOylation of IκBα
AU - Colomer-Lluch, Marta
AU - Serra-Moreno, Ruth
N1 - Publisher Copyright:
© 2017 American Society for Microbiology. All Rights Reserved.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
KW - Host-pathogen interactions
KW - Human immunodeficiency virus
KW - Innate immunity
KW - NF-κB
KW - Virology
UR - http://www.scopus.com/inward/record.url?scp=85016598071&partnerID=8YFLogxK
U2 - 10.1128/JVI.02098-16
DO - 10.1128/JVI.02098-16
M3 - Article
C2 - 28122985
AN - SCOPUS:85016598071
SN - 0022-538X
VL - 91
JO - Journal of Virology
JF - Journal of Virology
IS - 8
M1 - e02098-16
ER -