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

Alenquer, Marta; Vale-Costa, Sílvia; Etibor, Temitope Akhigbe; Ferreira, Filipe; Sousa, Ana Laura; Amorim, Maria João

http://hdl.handle.net/10400.7/916

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Authors

Alenquer, Marta

Vale-Costa, Sílvia

Etibor, Temitope Akhigbe

Ferreira, Filipe

Sousa, Ana Laura

Amorim, Maria João

Abstract(s)

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.

Keywords

A549 Cells Animals Cytosol Dogs Endoplasmic Reticulum Golgi Apparatus HEK293 Cells HeLa Cells Host-Pathogen Interactions Humans Influenza A virus Influenza, Human Madin Darby Canine Kidney Cells Protein Binding RNA, Viral Ribonucleoproteins Viral Proteins rab GTP-Binding Proteins Virus Assembly