Influenza Virus Induces Cholesterol-Enriched Endocytic Recycling Compartments for Budozone Formation via Cell Cycle-Independent Centrosome Maturation

Kawaguchi, Akiko; Hirohama, Mikako; Harada, Yoshimi; Osari, Suguru; Nagata, Kyosuke

doi:10.1371/journal.ppat.1005284

Cited by 41 publications

(56 citation statements)

References 51 publications

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“…Although vesicular clustering might, at some level, be in agreement with the reduction of recycling endosome efficiency that we report here, the existence of vesicles with double membranes suggests a distinct mechanism to rearrange membranes that we have not addressed and might be related to lipid metabolism. Interestingly, very recently, cholesterol has been shown to be enriched in recycling endosome vesicles (Kawaguchi et al, 2015). The formation of double-membraned vesicles is unclear; however, we found several U-shaped single-membraned vesicles (see Fig.…”

Section: Discussionmentioning

confidence: 49%

Influenza A virus ribonucleoproteins modulate host recycling by competing with Rab11 effectors

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Alenquer

Sousa

et al. 2016

Journal of Cell Science

127

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Influenza A virus assembly is an unclear process, whereby individual virion components form an infectious particle. The segmented nature of the influenza A genome imposes a problem to assembly because it requires packaging of eight distinct RNA particles (vRNPs). It also allows genome mixing from distinct parental strains, events associated with influenza pandemic outbreaks. It is important to public health to understand how segmented genomes assemble, a process that is dependent on the transport of components to assembly sites. Previously, it has been shown that vRNPs are carried by recycling endosome vesicles, resulting in a change of Rab11 distribution. Here, we describe that vRNP binding to recycling endosomes impairs recycling endosome function, by competing for Rab11 binding with family-interacting proteins, and that there is a causal relationship between Rab11 ability to recruit family-interacting proteins and Rab11 redistribution. This competition reduces recycling sorting at an unclear step, resulting in clustering of single- and double-membraned vesicles. These morphological changes in Rab11 membranes are indicative of alterations in protein and lipid homeostasis during infection. Vesicular clustering creates hotspots of the vRNPs that need to interact to form an infectious particle.Fundação para a Ciência e Tecnologia grants: (PTDC/IMI-MIC/1142/2012, SFRH/BPD/94204/2013, SFRH/BPD/62982/2009, IF/00899/2013); Fundação Calouste Gulbenkian; Instituto Gulbenkian de Ciência

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Section: Discussionmentioning

confidence: 49%

Influenza A virus ribonucleoproteins modulate host recycling by competing with Rab11 effectors

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Sousa

et al. 2016

Journal of Cell Science

127

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“…This notion is in agreement with vRNPs being found at the ER 16 . Interestingly, biogenesis of viral inclusions seems to be intertwined with deregulation of the ERC, which is coherent with a decrease in recycling of transferrin during infection 14,21 , and with Rab11 detection in the ER, as if it was re-directed to this organelle during infection 16 . Whether Rab11 vesicles are targeted to the ER to deliver or to collect vRNPs will be addressed in the future.…”

Section: Discussionmentioning

confidence: 63%

“…The process is very well-described for uninfected cells, with Rab11-GTP regulating ERC transport by recruiting molecular motors, tethers and SNARES to respectively drive, dock and fuse vesicles to the plasma membrane 18 . Despite initial reports that the functional role of Rab11 was to deliver vRNPs to the cell surface 10,12,17,19 , accumulating evidence analyzing Rab11 sub-cellular localization and non-abundancy in virions 14,16,20 , binding partners 14 and host transferrin recycling 14,21 strongly indicates that Rab11 is redirected and its function is impaired during IAV infection. In fact, it was demonstrated that vRNPs outcompeted Rab11 effectors for Rab11 binding, rendering the recycling process sub-optimal 14 .…”

Section: Main Textmentioning

confidence: 97%

Influenza A Virus Ribonucleoproteins Form Liquid Organelles at Endoplasmic Reticulum Exit Sites

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Sousa

et al. 2018

Preprint

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18Influenza A virus has an eight-partite RNA genome that during viral assembly forms a 19 supramolecular complex containing one copy of each RNA. Genome assembly is a selective 20 process driven by RNA-RNA interactions and is thought to lead to discrete punctate structures 21 scattered through the cytosol. Here, we show that contrary to the accepted view, formation of 22 these structures is not dependent on RNA-RNA interactions among distinct viral 23 ribonucleoproteins (vRNPs), as they assemble in cells expressing only one vRNP type. We 24 demonstrate that these viral inclusions display characteristics of liquid organelles, segregating 25 from the cytosol without a delimitating membrane, dynamically exchanging material, deforming 26 easily and adapting fast to hypotonic shock. We provide evidence that they develop close to the 27 Endoplasmic Reticulum Exit Sites (ERES), being dependent on continuous ER-Golgi vesicular 28cycling. We show that viral inclusions do not promote escape to interferon response, and 29 propose that they facilitate selected RNA-RNA interactions in a liquid environment of 30 concentrated vRNPs. 31 32 33 34 3 MAIN TEXT 35 Influenza A infections are serious threats to human health causing annual epidemics and 36 occasional pandemics 1 . The virus contains an eight-partite RNA genome, and each segment is 37 encapsidated as an individual viral ribonucleoprotein (vRNP) complex. vRNPs are composed of 38 single-stranded negative-sense RNA, with base paired terminal sequences originating a double 39 stranded RNA portion where the trimeric RNA-dependent RNA polymerase (RdRp), composed 40 of PB1, PB2 and PA, binds. The remaining sequence attaches several copies of unevenly-41 bound nucleoprotein (NP) 2 . The advantages of having a segmented genome are evident for 42 viral evolution 3 and for better gene expression control 4 , but increase the complexity of the 43 assembly of fully infectious virions 5-8 . 44 Viral assembly occurs at the plasma membrane and, in 80% of the cases, 8 distinct 45 vRNPs are packaged selectively into a budding membrane 9 . Seminal work established the 46 requirement of cis-acting and intersegment RNA-RNA interactions for the formation of this 47 supra-molecular complex (reviewed in 5-8 ). However, it is under debate if vRNPs reach the 48 plasma membrane already as complete genome bundles. 49Upon exiting the nucleus, where they replicate, vRNPs accumulate around the 50 microtubule organizing centre 10 and, subsequently, distribute throughout the cytoplasm 51 concentrating in discrete puncta that enlarge as infection progresses 10-14 . Each puncta 52 accommodates different vRNP segments with the diversity in vRNPs increasing proportionally to 53 the proximity of the plasma membrane 11,13 . Such observation led to the proposal that genome 54 assembly preceded vRNP packaging in budding virions by a process intimately linked with the 55 formation of the referred vRNP hotspots 6,11,[13][14][15] . Studies on the biogenesis of vRNP hotspots 56 showed that their formation requires...

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“…To compare formation of the putative assembly sites between dTHP1 cells and MDM, we used in situ proximity ligation assay (PLA). PLA allows for detection of two proteins localized within 40-nm distance of each other and has been used to visualize IAV assembly sites on the plasma membrane (38). In addition to measuring PLA signal between the given pair of proteins, we also co-stained cells for cell surface NA to identify infected cells.…”

Section: Resultsmentioning

confidence: 99%

A Defect in Influenza A Virus Particle Assembly Specific to Primary Human Macrophages

Bedi

Noda

Kawaoka

et al. 2017

Preprint

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18The primary target of Influenza A virus (IAV) is epithelial cells in the respiratory tract. In 19 contrast to epithelial cells, productive virus infection of most IAV strains is either 20 completely blocked or highly inefficient in macrophages. The exact nature of the defect 21 in IAV replication that leads to inefficient production of progeny virus particles in human 22 macrophages remains to be determined. In this study, we showed that primary human 42show that primary human MDM are not permissive to IAV replication due to a defect at 43 peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/213447 doi: bioRxiv preprint first posted online Nov. 2, 2017; the virus particle formation step. This defect is specific to primary human macrophages, 44 since a human monocyte-derived cell line differentiated into macrophage-like 45 morphology supports IAV particle formation. Further, comparison of these cell types 46suggests that the defect in virus particle assembly in MDM is at least partly due to 47 inefficient association between two viral glycoproteins, HA and M2, on the surface of 48 these cells. Overall, by identifying the viral protein interaction susceptible to cell-type-49 specific differences, our study suggests the possibility that the interactions between viral 50 components can be targeted to block IAV assembly in infected cells. 52 53peer-reviewed)

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Influenza Virus Induces Cholesterol-Enriched Endocytic Recycling Compartments for Budozone Formation via Cell Cycle-Independent Centrosome Maturation

Cited by 41 publications

References 51 publications

Influenza A virus ribonucleoproteins modulate host recycling by competing with Rab11 effectors

Influenza A virus ribonucleoproteins modulate host recycling by competing with Rab11 effectors

Influenza A Virus Ribonucleoproteins Form Liquid Organelles at Endoplasmic Reticulum Exit Sites

A Defect in Influenza A Virus Particle Assembly Specific to Primary Human Macrophages

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