RelAp43, a Member of the NF-κB Family Involved in Innate Immune Response against Lyssavirus Infection

PLoS Pathogens

Sophie Luco¹  Pierre-Olivier Vidalain¹  Robert Weil²  Frédéric Tangy²  Hervé Bourhy³  Olivier Delmas⁴ 

[1] Institut Pasteur, Unité Dynamique des Lyssavirus et Adaptation à l'Hôte, Paris, France;Institut Pasteur, Unité de Génomique virale et vaccination, Paris, France;Institut Pasteur, Unité de Signalisation moléculaire et Activation cellulaire, Paris, France;Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France

关键词: Transcription factors;    Small interfering RNAs;    HeLa cells;    Lyssavirus;    Messenger RNA;    Dimers (Chemical physics);    Luciferase;    Immunoprecipitation;   

DOI  :  10.1371/journal.ppat.1003060

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

NF-κB transcription factors are crucial for many cellular processes. NF-κB is activated by viral infections to induce expression of antiviral cytokines. Here, we identified a novel member of the human NF-κB family, denoted RelAp43, the nucleotide sequence of which contains several exons as well as an intron of the RelA gene. RelAp43 is expressed in all cell lines and tissues tested and exhibits all the properties of a NF-κB protein. Although its sequence does not include a transactivation domain, identifying it as a class I member of the NF-κB family, it is able to potentiate RelA-mediated transactivation and stabilize dimers comprising p50. Furthermore, RelAp43 stimulates the expression of HIAP1, IRF1, and IFN-β - three genes involved in cell immunity against viral infection. It is also targeted by the matrix protein of lyssaviruses, the agents of rabies, resulting in an inhibition of the NF-κB pathway. Taken together, our data provide the description of a novel functional member of the NF-κB family, which plays a key role in the induction of anti-viral innate immune response.

【 授权许可】

CC BY