Tracking Mechanisms of Viral Dissemination In Vivo
نویسندگان
چکیده
The zebrafish model allows in vivo investigations of virus-induced molecular processes at subcellular resolution.Viruses have evolved multiple strategies for disseminating over long distance, including by indoctrinating host cell types with high migration potential.Organoids derived from stem cells emerge as powerful alternatives to unravel new mechanisms viral dissemination. Dissemination and replication viruses into hosts is a multistep process where particles infect, navigate, indoctrinate various types. Viruses can reach tissues that are distant their infection site subverting ways are, sometimes, disruptive. Modeling these steps, appropriate resolution within animal models, cumbersome. Yet, mimicking vitro fails recapitulate the complexity cellular ecosystem. Here, we will discuss relevant platforms dissect programs governing dissemination briefly organoid ex alternatives. We focus on describe how it provides transparent window vivo. To disseminate hosts, pathogens had evolve navigate complex three-dimensional environments cannot be fully recapitulated two-dimensional monolayer culture. They deploy stratagems hijack resident stromal favor replication. While or useful, either through use organoids tissue explants (Box 1), established models systems unraveling favoring Cell biologists adapted platforms, such embryos mice, develop exciting approaches allowing dissection foster spreading. More recently, culture human embryonic induced pluripotent been developed study multidimensional settings 1). bacterial was recently reviewed [1.Torraca V. Mostowy S. Zebrafish infection: pathogenesis biology.Trends Biol. 2018; 28: 143-156Abstract Full Text PDF PubMed Scopus (86) Google Scholar], aim here discussing recent work related biology virus vivo, list current technical limitations, propose future developments.Box 1Alternatives Animal ModelsWith ethical concerns regarding research, non-animal 3D developed. 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Organoid assembloid technologies investigating crosstalk brain disease.Trends 2020; 30: 133-143Abstract (101) Scholar]. Nature, size, genetics, imaging, reproducibility properties justifying why acclaimed. Recently, instance, intestinal were used SARS-CoV-2 intracellular [45.Lamers M.M. al.SARS-CoV-2 productively infects gut enterocytes.Science. 369: 50-54Crossref (1010) observed double membrane vesicles, Golgi apparatus, inside endomembrane system, while secretion occurring both apical basolateral side (Figure which consistent observation shed feces infected [46.Wu al.Prolonged presence RNA faecal samples.Lancet Gastroenterol. Hepatol. 5: 434-435Abstract (1044) Organoids also adequately apoptosis division, exemplified ZIKV-infected cerebral [47.Watanabe M. al.Self-organized human-specific features predict effective drugs combat Zika infection.Cell Rep. 2017; 21: 517-532Abstract (225) Scholar,48.Tang H. cortical neural progenitors attenuates growth.Cell Stem Cell. 2016; 18: 587-590Abstract (936) should prove useful variety other As opposed offer unique working tissue-like conditions. Although not adaptive immune responses interorgan physiopathology, they considered animal-free address greater detail. With Viral refers ability tissular compartments remotely located initial site. This includes fluid-to-tissue, tissue-to-fluid, tissue-to-tissue dissemination, addition cell-to-cell transmission [2.Cifuentes-Munoz N. al.Direct respiratory viruses: fast lanes.PLoS Pathog. 14e1007015Crossref (60) Scholar,3.Graw F. Perelson A.S. spread.Annu. Rev. Virol. 3: 555-572Crossref (58) Such large-scale transitional stages require builds well-orchestrated subversion mechanisms, disruptive or, contrario, quiet. any case, critical decipher involved multiorgan scale and, this end, instrumental approaches. A common way afferent fluid canals naturally irrigate organism. bloodstream perfect culprit track may occur [4.Ayala-Nunez N.V. Gaudin R. journey brain: considerations developments.PLoS 16e1008434Crossref (15) embryo (until 2.5 days postfertilization) larvae 6 weeks (Danio rerio) very toward organs [5.Levraud J.P. al.Through looking glass: witnessing host-virus interplay zebrafish.Trends 22: 490-497Abstract (36) Indeed, genetic manipulation straightforward fluorescent fish lines tracking (endothelial, cells, etc.) readily available [6.Ruzicka L. al.The Information Network: support non-coding genes, richer gene ontology annotations Alliance Genome Resources.Nucleic Acids Res. 47: D867-D873Crossref (93) displays innate vertebrate-type immunity (see Glossary). addition, although might less developments now immunocompromised strains, xenotransplantation patient samples contribution key elements pathophysiology [7.Fazio al.Zebrafish avatars cancer precision Cancer. 20: 263-273Crossref (104) Moreover, major advantage high-throughput screening [8.Varela al.Modelling infections zebrafish: response antiviral research.Antivir. 59-68Crossref (57) feature ethically impossible perform mice. strategy currently identify potent small molecules, toxicity, active against severe acute syndrome coronavirus 2 (SARS-CoV-2), causative agent 2019 (COVID-19) 2) [9.Galindo-Villegas J. drug model: strong ally Covid-19.Front. 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Commun. 4430Crossref Scholar].Box 2Zebrafish Context SARS-Co-2 PandemicNumerous labs rushing SARS-CoV-2, no reports formally published date, suggesting causing COVID-19 vigorously infect zebrafish. receptor angiotensin-converting enzyme (ACE-2) factor TMPRSS2 protease show 69% 54% similarities proteins (pairwise sequence alignment EMBOSS Needle [49.Madeira EMBL-EBI search analysis tools APIs 2019.Nucleic W636-W641Crossref (2706) Scholar]). Thus, engineered zebrafish-expressing receptors could promote susceptibility SARS-CoV-2. One think difficult organism deprived lungs. However, well-known virus, influenza shown cause significant pathological phenotypes [21.Gabor K.A. al.Influenza recapitulates mammalian sensitivity anti-influenza treatment.Dis. 7: 1227-1237Crossref (53) thus, still hold promise fight COVID-19. Numerous Studies extensively [14.Zou P.F. 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Tg(fli1:GFP) line exhibiting ideal process, infectious necrosis strongly disrupts vessels [24.Ludwig al.Whole-body vascular endothelium primary target 2011; 7e1001269Crossref lesser extent, vasculature larvae, leading authors later found infecting central nervous (CNS) independently infection. represents one first our knowledge routes neuroinvasion, made possible thanks advanced invasion CNS (ZIKV) investigated interferon-?/? (IFNAR)-deficient outcome evident [25.Papa M.P. infects, activates, crosses microvascular without barrier disruption.Front. 8: 2557Crossref (71) nicely showed blood–brain (BBB) disrupted, remains determined whether reaches release, transcytosis, transinfection information requires high-resolution intravital technically 3).Box 3Beyond Zebrafish: Mouse Model Study DisseminationThe mouse virus–host interactions [50.Sewald X. Visualizing multi-photon microscopy.Viruses. 337Crossref Scholar]; however, more than because tissues, microscopy (IVM) specific according organ imaged. detailed protocol IVM lung released [51.Ueki al.Multicolor two-photon upon IMPRESS.Nat. Protoc. 15: 1041-1065Crossref Scholar] infection, targeting organs. humanized nontrivial disease. having closely humans better infections. pioneering lymph nodes monitor immunodeficiency (HIV-1) T [52.Murooka T.T. al.HIV-infected migratory vehicles dissemination.Nature. 2012; 490: 283-287Crossref (240) after CD169-dependent transfer sinus-lining [53.Sewald al.Retroviruses CD169-mediated trans-infection permissive lymphocytes establish infection.Science. 2015; 350: 563-567Crossref (129) Visualization fluorescently tagged vesicular stomatitis live leukocytes transporting oncolytic tumors [54.Naumenko al.Visualizing virus-host microscopy.Mol. Ther. Oncolytics. 14-27Abstract (17) These underlying proposed. Murooka colleagues intriguingly HIV-infected exhibited unusually elongated, thin, branched trailing edges must result dramatic cytoskeletal rearrangements remain characterized Using electron tomography bone marrow description several scenarios HIV cell–cell further depicted 1) [55.Ladinsky M.S. al.Mechanisms HIV-1-infected BLT mice.Elife. 8e46916Crossref again, identified. vaccinia (VACV) enhance rapid directed motility EGFR [56.Beerli al.Vaccinia hijacks signalling spread motility.Nat. 216-225Crossref (45) highlight inhibitors factors ADAM10, EGFR, MAPK, FAK reduced radial velocity directional depletion viral-encoded protein VGF decreases migration. revealed responsible lesion formation ear pinnae. Because focal formation, envision VACV controls dynamics Finally, Drosophila melanogaster understand Nora notably creation transgenic reporter emit fluorescence [57.Ekstrom J.O. Hultmark D. detection melanogaster.Sci. 6: 26250Crossref (5) flies relevance would rightfully questionable. subtler method invade remote organs, consists hiding components, platelets monocytes [13.Ayala-Nunez Scholar,26.Simon A.Y. al.Dengue binding platelets.Blood. 126: 378-385Crossref (112) conferring protective shell them. When hiding, replicate cell, just carried compartment cell. latter strategy, hazardous need disseminate, being degradative endolysosomes [27.Robinson al.Viral journeys highways.Cell. Life Sci. 75: 3693-3714Crossref (52) Nevertheless, benefit possibility hitch ride incognito distances, opening door long-range It sneakily cross barriers, usually impermeable microbes, disrupting inducing response. phenomenon referred Trojan horse hypothesis Scholar,28.Santiago-Tirado F.H. Doering T.L. False friends: phagocytes horses microbial infections.PLoS 13e1006680Crossref (33) described 35 years ago [29.Peluso visna monocytes.Virology. 1985; 147: 231-236Crossref (273) Recent highlighted ZIKV monocytes. Tracking behavior mechanistic intravascular arrest ZIKV-exposed increased when compared nonexposed counterparts. findings correlated expression molecules surface monocytes, promotes attachment cells. Interestingly, only favors stimulates extravasation, step experimental originally [30.Follain al.Fluids mechanics tumour transit: shaping metastasis.Nat. 107-124Crossref (159) highlighting successful adaptation designed acknowledge limitations long-term there evidence efficiently zebrafish, taken relative permissiveness xenografts investigate across wall Similarly, cytomegalovirus (HCMV) induce [31.Smith al.Human induces differentiation persistence.J. 2004; 78: 4444-4453Crossref (176) HCMV [32.Cazorla-Vazquez cytomegaloviral multifunctional kinase pUL97 impairs increases mortality.Sci. 7219Crossref (4) could, injecting HCMV-infected context. Transplanting adult possible, (i.e., rag2 mutant [33.Tang Q. al.Optimized transplantation zebrafish.Nat. Methods. 821-824Crossref envisioned optically cleared lack T, B, natural killer prkdc–/–, il2rga–/– [34.Yan engrafted therapy immunodeficient zebrafish.Cell. 177: 1903-1914Abstract (141) comes drawback allow understanding shapes illness, medicine [35.Goody M.F. al.Studying zebrafish.Dev. Comp. 46: 84-95Crossref (35) benefits analyses overlooked. resolution, addressing attachment, rolling, wall, drastic actin rearrangements, influence sheer stress Scholar,5.Levraud Scholar,12.Passoni needed Outstanding Questions). For example, provide clear adults. particular, platform correlative nanoscale thereby membranous rearrangement [36.Wolff al.Double-membrane vesicles replication.Trends June 11, https://doi.org/10.1016/j.tim.2020.05.009)Abstract (130) Correlative light (CLEM) uptake extracellular [37.Hyenne fate spatiotemporal embryo.Dev. 48: 554-572Abstract (110) similar many aspects (size, morphology, content, particles. Alternatively, apply CLEM [38.Karreman al.Intravital microscopy: life nanoscale.Trends 26: 848-863Abstract (68) capture discovery viruses. reported strain expresses GFP interferon-stimulated promoter. discovering testing impact vertebrate [39.Balla K.M. al.Linking visualized during infections.Curr. 2092-2103Abstract (20) Scholar].Outstanding QuestionsCan become dissemination?Can super-resolution applied (or zebrafish) resolution?Will replace animal-based future?Can single particle spatio-temporal resolution? Can dissemination? Will future? thank all members Labs helpful discussions. funded institutional funds CNRS R.G INSERM University Strasbourg enveloped single-stranded positive-sense (Togaviridae family). object (cellular, subcellular) sample photonic microscopy. fibers forming ‘net’ primarily composed neutrophils. phenomenons living organisms. double-stranded (Herpesviridae nonenveloped (Caliciviridae negative-sense (Rhabdoviridae (Orthomyxoviridae nonspecific defense immediate long-lasting pathogen. active. part attacks lipid bilayer membranes. (Coronaviridae (Poxviridae tissues. (Flaviviridae
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ژورنال
عنوان ژورنال: Trends in Cell Biology
سال: 2021
ISSN: ['0962-8924', '1879-3088']
DOI: https://doi.org/10.1016/j.tcb.2020.09.005