Influenza A virus ribonucleoproteins form liquid organelles at endoplasmic reticulum exit sites

• Published in: Nature communications 2019-04, Vol.10 (1), p.1629-1629, Article 1629
• Main Authors: Alenquer, Marta, Vale-Costa, Sílvia, Etibor, Temitope Akhigbe, Ferreira, Filipe, Sousa, Ana Laura, Amorim, Maria João
• Format: Article
• Language: English
• Subjects: 13/106; 13/109; 13/31; 14/1; 14/19; 14/28; 14/32; 14/34; 14/5; 14/63; 42/70; 45/77; 631/57/2268; 631/80/304; 692/699/255/1578; 82/29; 82/80; A549 Cells; Animals; Assembly; Cytosol; Cytosol - metabolism; Cytosol - virology; Dogs; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - virology; Environmental changes; Genomes; Golgi apparatus; Golgi Apparatus - metabolism; Golgi Apparatus - virology; HEK293 Cells; HeLa Cells; Host-Pathogen Interactions; Humanities and Social Sciences; Humans; Inclusion bodies; Inclusions; Influenza; Influenza A; Influenza A virus - pathogenicity; Influenza A virus - physiology; Influenza, Human - pathology; Influenza, Human - virology; Interferon; Madin Darby Canine Kidney Cells; multidisciplinary; Organelles; Pandemics; Protein Binding; rab GTP-Binding Proteins - metabolism; Ribonucleic acid; Ribonucleoproteins; Ribonucleoproteins - metabolism; RNA; RNA viruses; RNA, Viral - metabolism; Science; Science (multidisciplinary); Viral Proteins - metabolism; Virus Assembly; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09549-4

Influenza A virus has an eight-partite RNA genome that during viral assembly forms a complex containing one copy of each RNA. Genome assembly is a selective process driven by RNA-RNA interactions and is hypothesized to lead to discrete punctate structures scattered through the cytosol. Here, we show that contrary to the accepted view, formation of these structures precedes RNA-RNA interactions among distinct viral ribonucleoproteins (vRNPs), as they assemble in cells expressing only one vRNP type. We demonstrate that these viral inclusions display characteristics of liquid organelles, segregating from the cytosol without a delimitating membrane, dynamically exchanging material and adapting fast to environmental changes. We provide evidence that viral inclusions develop close to endoplasmic reticulum (ER) exit sites, depend on continuous ER-Golgi vesicular cycling and do not promote escape to interferon response. We propose that viral inclusions segregate vRNPs from the cytosol and facilitate selected RNA-RNA interactions in a liquid environment. Influenza A virus forms cytosolic inclusions containing viral ribonucleoproteins. Here, the authors show that viral inclusions form juxtaposed the endoplasmic reticulum and have liquid properties, likely constituting sites of assembly of epidemic and pandemic influenza genomes.