Myoferlin is a component of late-stage vRNP trafficking vesicles for enveloped RNA viruses

Abstract

Abstract The Rab11 endosomal recycling pathway is exploited by important respiratory RNA viruses such as IAV and RSV, aiding viral egress from the apical surface of polarized epithelial cells. Late in infection, Rab11-containing vesicles specifically transport viral ribonucleoprotein (vRNP) complexes towards the cell surface before packaging and budding. Rather than employing traditional Rab11-positive recycling endosomes, virus-infected cells generate remodelled Rab11-containing vesicles, as observed during IAV infection. Besides Rab11, no other conserved host co-factors have been identified among these various vRNP trafficking vesicles. Here we discover and confirm myoferlin’s association with IAV vRNPs in the cytoplasm and colocalisation with Rab11 during late stages of infection. We also find that this role is conserved in late-stage vRNP trafficking of other viruses, including RSV and SeV. Myoferlin likely recruits the EHD family of proteins, which are involved in endosomal biogenesis, to these unique vRNP trafficking endosomes, highlighting myoferlin’s pivotal role in viral replication.