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RANBP2 (also known as Nup358) is the largest nucleoporin of the nuclear pore complex (NPC), where it constitutes the main component of the cytoplasmic…

Evidence is growing that some HIV-infected infants, if given antiretroviral drugs early in life, are able to suppress their viral loads to undetectable levels and then come off the medicine.

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Conventional cerebral organoids do not contain microglia, which must be added. We propose recommendations to assess microglial immunocompetence using quantitative approaches and stringent statist...

Vaccine Integrity Project intends to provide scientific responses to ill-founded vaccine moves

Acute Necrotizing Encephalopathy Multidisciplinary Outreach Network Connecting Families, Clinicians and Scientists around a Rare Genetic Disease

Influenza virus infections can cause severe complications such as Acute Necrotizing Encephalopathy (ANE), which is characterised by rapid onset pathological inflammation following febrile infection. H...

Influenza virus infections can cause severe complications such as Acute Necrotizing Encephalopathy (ANE), which is characterised by rapid onset pathological inflammation following febrile infection. Heterozygous dominant mutations in the nucleoporin RANBP2/Nup358 predispose to influenza-triggered ANE1. The aim of our study was to determine whether RANBP2 plays a role in IAV-triggered inflammatory responses. We found that the depletion of RANBP2 in a human airway epithelial cell line increased IAV genomic replication by favouring the import of the viral polymerase subunits, PB1, PB2 and PA, and promoted an abnormal accumulation of some viral segments in the cytoplasm. In human primary macrophages, this corroborated with an enhanced production of the pro-inflammatory chemokines CXCL8, CXCL10, CCL2, CCL3 and CCL4. Then, using CRISPR-Cas9 knock-in for the ANE1 disease variant RANBP2-T585M, we demonstrated that the point mutation is sufficient to drive CXCL10 expression following activation downstream of RIG-I and leads to a redistribution of RANBP2 away from the nuclear pore. Together, our results reveal that RANBP2 regulates influenza RNA replication and nuclear export, triggering hyper-inflammation, offering insight into ANE pathogenesis. ### Competing Interest Statement The authors have declared no competing interest.