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

doi:10.1038/s41467-019-09549-4

Cited by 130 publications

(167 citation statements)

References 70 publications

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“…Based on these previous data and our current work, we speculate that intracellular transport and assembly of IAV vRNP segments requires a membrane scaffold either in the form of Rab11A-RE or the ER, and this membrane promiscuity may provide an advantage for vRNP segmentsegment assembly. Recent work has also suggested that vRNP exits the ER in liquid-phase organelles 60 . Therefore, additional work examining the intracellular movement of individual vRNP segments and ER membranes within a single cell is needed to elucidate the importance of dynamic membranous scaffolds during IAV infection.…”

Section: Discussionmentioning

confidence: 99%

Quantitative live cell imaging reveals influenza virus manipulation of Rab11A transport through reduced dynein association

et al. 2020

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Assembly of infectious influenza A viruses (IAV) is a complex process involving transport from the nucleus to the plasma membrane. Rab11A-containing recycling endosomes have been identified as a platform for intracellular transport of viral RNA (vRNA). Here, using high spatiotemporal resolution light-sheet microscopy (~1.4 volumes/second, 330 nm isotropic resolution), we quantify Rab11A and vRNA movement in live cells during IAV infection and report that IAV infection decreases speed and increases arrest of Rab11A. Unexpectedly, infection with respiratory syncytial virus alters Rab11A motion in a manner opposite to IAV, suggesting that Rab11A is a common host component that is differentially manipulated by respiratory RNA viruses. Using two-color imaging we demonstrate co-transport of Rab11A and IAV vRNA in infected cells and provide direct evidence that vRNA-associated Rab11A have altered transport. The mechanism of altered Rab11A movement is likely related to a decrease in dynein motors bound to Rab11A vesicles during IAV infection.

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Section: Discussionmentioning

confidence: 99%

Quantitative live cell imaging reveals influenza virus manipulation of Rab11A transport through reduced dynein association

et al. 2020

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“…Liquid–liquid phase separation (LLPS) occurs in cells, plays a role during infections, and is fundamental to amphiphilic self‐assembly processes . Liquid–liquid‐separated precursor species, on the other hand, also form in inorganic systems, for example, in oxide melts and aqueous salt solutions.…”

Section: Figurementioning

confidence: 99%

Stable Prenucleation Calcium Carbonate Clusters Define Liquid–Liquid Phase Separation

et al. 2020

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Liquid–liquid phase separation (LLPS) is an intermediate step during the precipitation of calcium carbonate, and is assumed to play a key role in biomineralization processes. Here, we have developed a model where ion association thermodynamics in homogeneous phases determine the liquid–liquid miscibility gap of the aqueous calcium carbonate system, verified experimentally using potentiometric titrations, and kinetic studies based on stopped‐flow ATR‐FTIR spectroscopy. The proposed mechanism explains the variable solubilities of solid amorphous calcium carbonates, reconciling previously inconsistent literature values. Accounting for liquid–liquid amorphous polymorphism, the model also provides clues to the mechanism of polymorph selection. It is general and should be tested for systems other than calcium carbonate to provide a new perspective on the physical chemistry of LLPS mechanisms based on stable prenucleation clusters rather than un‐/metastable fluctuations in biomineralization, and beyond.

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“…For example, the cytoplasmic inclusions that harbor vesicular stomatitis virus (VSV) RNA synthesis demonstrate several liquid-like properties, including the ability to fuse together, and the rapid exchange of viral polymerase complex protein P between these inclusions and the cytoplasm [91]. In addition, influenza A virus (IAV) ribonucleoproteins form liquid inclusions at endoplasmic reticulum exit sites, suggesting that LLPS may play a role in the early stages of IAV assembly [92]. Furthermore, the ability of the Hendra virus V protein to form liquid hydrogels that may contribute to cellular toxicity was recently demonstrated [93].…”

Section: Biophysical Processes In Replication Compartment Formationmentioning

confidence: 99%

Replication Compartments of DNA Viruses in the Nucleus: Location, Location, Location

Charman

Weitzman

2020

Viruses

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DNA viruses that replicate in the nucleus encompass a range of ubiquitous and clinically important viruses, from acute pathogens to persistent tumor viruses. These viruses must co-opt nuclear processes for the benefit of the virus, whilst evading host processes that would otherwise attenuate viral replication. Accordingly, DNA viruses induce the formation of membraneless assemblies termed viral replication compartments (VRCs). These compartments facilitate the spatial organization of viral processes and regulate virus-host interactions. Here, we review advances in our understanding of VRCs. We cover their initiation and formation, their function as the sites of viral processes, and aspects of their composition and organization. In doing so, we highlight ongoing and emerging areas of research highly pertinent to our understanding of nuclear-replicating DNA viruses.Viruses 2020, 12, 151 2 of 20 The Initiation and Formation of Replication CompartmentsDNA viruses that replicate in the nucleus exhibit a diverse array of strategies to complete their replication cycle and ultimately produce progeny virions. Despite their many differences, the strategies employed by DNA viruses to initiate productive infection and establish VRCs share many features in common. Indeed, it is likely that all DNA viruses that replicate in the nucleus form VRCs. Following penetration of the host cell and the transport of viral capsids/cores, viral DNA genomes enter the nucleus, where they begin a program of temporally regulated gene expression that initiates productive infection [1,2]. Early gene products include viral proteins required to manipulate the host-cell environment and replicate the viral genome. Viral replication proteins interact with the viral genome and initiate genome replication leading to VRC formation, which is often in concert with certain co-opted host proteins. However, these viruses must overcome several challenges to form VRCs successfully. Firstly, incoming genomes must avoid cellular intrinsic antiviral defenses and homeostatic regulatory pathways such as elements of the DNA damage response (DDR) that respond to the presence of foreign DNA and act to suppress viral gene expression [3][4][5][6][7][8][9][10]. Secondly, VRCs typically form at specific sites within the nucleus, suggesting that viral genomes need to be targeted to these sites in order to initiate VRC formation [6,11,12]. Furthermore, it has been hypothesized that the formation and growth of VRCs may require manipulation of the nuclear environment and the re-organization of host chromatin to overcome the spatial restraints of the nucleus [11][12][13][14][15]. In this section, we review key features of VRC initiation and highlight some major challenges to VRC formation. Interplay between Viral Replication Compartment Formation and Promyelocytic Leukemia Protein Nuclear BodiesA common theme amongst many nuclear-replicating DNA viruses is initiation of VRCs at sites in close proximity to promyelocytic leukemia protein (PML) nuclear bodies (NBs). Since the dis...

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

Cited by 130 publications

References 70 publications

Quantitative live cell imaging reveals influenza virus manipulation of Rab11A transport through reduced dynein association

Quantitative live cell imaging reveals influenza virus manipulation of Rab11A transport through reduced dynein association

Stable Prenucleation Calcium Carbonate Clusters Define Liquid–Liquid Phase Separation

Replication Compartments of DNA Viruses in the Nucleus: Location, Location, Location

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