دورية أكاديمية

Antiviral responses are shaped by heterogeneity in viral replication dynamics.

التفاصيل البيبلوغرافية
العنوان: Antiviral responses are shaped by heterogeneity in viral replication dynamics.
المؤلفون: Bruurs LJM; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Müller M; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Schipper JG; Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands., Rabouw HH; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.; Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands., Boersma S; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., van Kuppeveld FJM; Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands., Tanenbaum ME; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands. m.tanenbaum@hubrecht.eu.; Department of Bionanoscience, Delft University of Technology, Delft, the Netherlands. m.tanenbaum@hubrecht.eu.
المصدر: Nature microbiology [Nat Microbiol] 2023 Nov; Vol. 8 (11), pp. 2115-2129. Date of Electronic Publication: 2023 Oct 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101674869 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2058-5276 (Electronic) Linking ISSN: 20585276 NLM ISO Abbreviation: Nat Microbiol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Publishing Group, [2016]-
مواضيع طبية MeSH: Virus Replication* , Virus Diseases*, Humans ; Signal Transduction ; Encephalomyocarditis virus/physiology ; Antiviral Agents
مستخلص: Antiviral signalling, which can be activated in host cells upon virus infection, restricts virus replication and communicates infection status to neighbouring cells. The antiviral response is heterogeneous, both quantitatively (efficiency of response activation) and qualitatively (transcribed antiviral gene set). To investigate the basis of this heterogeneity, we combined Virus Infection Real-time IMaging (VIRIM), a live-cell single-molecule imaging method, with real-time readouts of the dsRNA sensing pathway to analyse the response of human cells to encephalomyocarditis virus (EMCV) infection. We find that cell-to-cell heterogeneity in viral replication rates early in infection affect the efficiency of antiviral response activation, with lower replication rates leading to more antiviral response activation. Furthermore, we show that qualitatively distinct antiviral responses can be linked to the strength of the antiviral signalling pathway. Our analyses identify variation in early viral replication rates as an important parameter contributing to heterogeneity in antiviral response activation.
(© 2023. The Author(s).)
References: O’Neill, L. A. J. & Bowie, A. G. Sensing and signaling in antiviral innate immunity. Curr. Biol. 20, R328–R333 (2010). (PMID: 2039242610.1016/j.cub.2010.01.044)
Schoggins, J. W. & Rice, C. M. Interferon-stimulated genes and their antiviral effector functions. Curr. Opin. Virol. 1, 519–525 (2011). (PMID: 22328912327438210.1016/j.coviro.2011.10.008)
Mesev, E. V., LeDesma, R. A. & Ploss, A. Decoding type I and III interferon signalling during viral infection. Nat. Microbiol. 4, 914–924 (2019). (PMID: 30936491655402410.1038/s41564-019-0421-x)
Postal, M. et al. Type I interferon in the pathogenesis of systemic lupus erythematosus. Curr. Opin. Immunol. 67, 87–94 (2020). (PMID: 33246136805482910.1016/j.coi.2020.10.014)
Lee, J. S. & Shin, E.-C. The type I interferon response in COVID-19: implications for treatment. Nat. Rev. Immunol. 20, 585–586 (2020). (PMID: 32788708882444510.1038/s41577-020-00429-3)
Sposito, B. et al. The interferon landscape along the respiratory tract impacts the severity of COVID-19. Cell 184, 4953–4968.e16 (2021). (PMID: 837382110.1016/j.cell.2021.08.016)
Nelemans, T. & Kikkert, M. Viral innate immune evasion and the pathogenesis of emerging RNA virus infections. Viruses 11, 961 (2019). (PMID: 31635238683242510.3390/v11100961)
Crow, Y. J. Type I interferonopathies: a novel set of inborn errors of immunity. Ann. N. Y. Acad. Sci. 1238, 91–98 (2011). (PMID: 2212905610.1111/j.1749-6632.2011.06220.x)
Crow, Y. J. & Stetson, D. B. The type I interferonopathies: 10 years on. Nat. Rev. Immunol. https://doi.org/10.1038/s41577-021-00633-9 (2021). (PMID: 10.1038/s41577-021-00633-9346711228527296)
Pichlmair, A. et al. Activation of MDA5 requires higher-order RNA structures generated during virus infection. J. Virol. 83, 10761–10769 (2009). (PMID: 19656871275314610.1128/JVI.00770-09)
Dias Junior, A. G., Sampaio, N. G. & Rehwinkel, J. A. Balancing act: MDA5 in antiviral immunity and autoinflammation. Trends Microbiol. 27, 75–85 (2019). (PMID: 3020151210.1016/j.tim.2018.08.007)
Rehwinkel, J. & Gack, M. U. RIG-I-like receptors: their regulation and roles in RNA sensing. Nat. Rev. Immunol. 20, 537–551 (2020). (PMID: 32203325709495810.1038/s41577-020-0288-3)
Andersen, J., VanScoy, S., Cheng, T.-F., Gomez, D. & Reich, N. C. IRF-3-dependent and augmented target genes during viral infection. Genes Immun. 9, 168–175 (2008). (PMID: 1809470910.1038/sj.gene.6364449)
Savitsky, D., Tamura, T., Yanai, H. & Taniguchi, T. Regulation of immunity and oncogenesis by the IRF transcription factor family. Cancer Immunol. Immunother. 59, 489–510 (2010). (PMID: 2004943110.1007/s00262-009-0804-6)
Schoggins, J. W. Interferon-stimulated genes: what do they all do? Annu. Rev. Virol. 6, 567–584 (2019). (PMID: 3128343610.1146/annurev-virology-092818-015756)
Schneider, W. M., Chevillotte, M. D. & Rice, C. M. Interferon-stimulated genes: a complex web of host defenses. Annu. Rev. Immunol. 32, 513–545 (2014). (PMID: 24555472431373210.1146/annurev-immunol-032713-120231)
Grandvaux, N. et al. Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. J. Virol. 76, 5532–5539 (2002). (PMID: 1199198113705710.1128/JVI.76.11.5532-5539.2002)
Lei, X., Xiao, X. & Wang, J. Innate immunity evasion by enteroviruses: insights into virus–host interaction. Viruses 8, 22 (2016). (PMID: 26784219472858210.3390/v8010022)
Feng, Q., Langereis, M. A. & van Kuppeveld, F. J. M. Induction and suppression of innate antiviral responses by picornaviruses. Cytokine Growth Factor Rev. 25, 577–585 (2014). (PMID: 25086453717259510.1016/j.cytogfr.2014.07.003)
Rand, U. et al. Uncoupling of the dynamics of host–pathogen interaction uncovers new mechanisms of viral interferon antagonism at the single-cell level. Nucleic Acids Res. 42, e109 (2014). (PMID: 24895433411775010.1093/nar/gku492)
Doğanay, S. et al. Single-cell analysis of early antiviral gene expression reveals a determinant of stochastic IFNB1 expression. Integr. Biol. 9, 857–867 (2017). (PMID: 10.1039/C7IB00146K)
Zhao, M., Zhang, J., Phatnani, H., Scheu, S. & Maniatis, T. Stochastic expression of the interferon-β gene. PLoS Biol. 10, e1001249 (2012). (PMID: 22291574326547110.1371/journal.pbio.1001249)
Drayman, N., Patel, P., Vistain, L. & Tay, S. HSV-1 single-cell analysis reveals the activation of anti-viral and developmental programs in distinct sub-populations. eLife 8, e46339 (2019). (PMID: 31090537657048210.7554/eLife.46339)
Patil, S. et al. Single-cell analysis shows that paracrine signaling by first responder cells shapes the interferon-β response to viral infection. Sci. Signal. 8, ra16 (2015). (PMID: 2567020410.1126/scisignal.2005728)
Zawatzky, R., De Maeyer, E. & De Maeyer-Guignard, J. Identification of individual interferon-producing cells by in situ hybridization. Proc. Natl Acad. Sci. USA 82, 1136–1140 (1985). (PMID: 385625139720910.1073/pnas.82.4.1136)
Sjaastad, L. E. et al. Distinct antiviral signatures revealed by the magnitude and round of influenza virus replication in vivo. Proc. Natl Acad. Sci. USA 115, 9610–9615 (2018). (PMID: 30181264615662910.1073/pnas.1807516115)
Wimmers, F. et al. Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells. Nat. Commun. 9, 3317 (2018). (PMID: 30127440610222310.1038/s41467-018-05784-3)
Rand, U. et al. Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response. Mol. Syst. Biol. 8, 584 (2012). (PMID: 22617958337799210.1038/msb.2012.17)
Talemi, S. R. & Höfer, T. Antiviral interferon response at single-cell resolution. Immunol. Rev. 285, 72–80 (2018). (PMID: 3012920310.1111/imr.12699)
Jones, J. E., Le Sage, V. & Lakdawala, S. S. Viral and host heterogeneity and their effects on the viral life cycle. Nat. Rev. Microbiol. 19, 272–282 (2021). (PMID: 3302430910.1038/s41579-020-00449-9)
Guo, F. et al. Single-cell virology: on-chip investigation of viral infection dynamics. Cell Rep. 21, 1692–1704 (2017). (PMID: 29117571568946010.1016/j.celrep.2017.10.051)
Schulte, M. B. & Andino, R. Single-cell analysis uncovers extensive biological noise in poliovirus replication. J. Virol. 88, 6205–6212 (2014). (PMID: 2464845410.1128/JVI.03539-13)
Russell, A. B., Trapnell, C. & Bloom, J. D. Extreme heterogeneity of influenza virus infection in single cells. eLife 7, e32303 (2018). (PMID: 29451492582627510.7554/eLife.32303)
Fiege, J. K. et al. Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium. PLoS Pathog. 17, e1009292 (2021). (PMID: 33507952787226110.1371/journal.ppat.1009292)
O’Neal, J. T. et al. West Nile virus-inclusive single-cell RNA sequencing reveals heterogeneity in the Type I interferon response within single cells. J. Virol. 93, e01778-18 (2019). (PMID: 30626670640146810.1128/JVI.01778-18)
Martin, B. E., Harris, J. D., Sun, J., Koelle, K. & Brooke, C. B. Cellular co-infection can modulate the efficiency of influenza A virus production and shape the interferon response. PLoS Pathog. 16, e1008974 (2020). (PMID: 33064776759291810.1371/journal.ppat.1008974)
Boersma, S. et al. Translation and replication dynamics of single RNA viruses. Cell 183, 1930–1945.e23 (2020). (PMID: 33188777766454410.1016/j.cell.2020.10.019)
Satoh, T. et al. LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. Proc. Natl Acad. Sci. USA 107, 1512–1517 (2010). (PMID: 20080593282440710.1073/pnas.0912986107)
Deddouche, S. et al. Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells. eLife 3, e01535 (2014). (PMID: 24550253396786110.7554/eLife.01535)
Fout, G. S. & Simon, E. H. Antiviral activities directed against wild-type and interferon-sensitive mengovirus. J. Gen. Virol. 64, 1543–1555 (1983). (PMID: 619098910.1099/0022-1317-64-7-1543)
Hato, S. V. et al. The mengovirus leader protein blocks interferon-alpha/beta gene transcription and inhibits activation of interferon regulatory factor 3. Cell Microbiol. 9, 2921–2930 (2007). (PMID: 1799104810.1111/j.1462-5822.2007.01006.x)
Tanenbaum, M. E., Gilbert, L. A., Qi, L. S., Weissman, J. S. & Vale, R. D. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell 159, 635–646 (2014). (PMID: 25307933425260810.1016/j.cell.2014.09.039)
Huang, L. et al. Encephalomyocarditis virus 3C protease attenuates type I interferon production through disrupting the TANK-TBK1-IKKε-IRF3 complex. Biochem. J. 474, 2051–2065 (2017). (PMID: 2848737810.1042/BCJ20161037)
Li, L. et al. Encephalomyocarditis virus 2C protein antagonizes interferon-β signaling pathway through interaction with MDA5. Antivir. Res. 161, 70–84 (2019). (PMID: 3031263710.1016/j.antiviral.2018.10.010)
Han, Y. et al. Encephalomyocarditis virus abrogates the interferon beta signaling pathway via its structural protein VP2. J. Virol. 95, e01590-20 (2021). (PMID: 33328314809493610.1128/JVI.01590-20)
Bandyopadhyay, S. K., Leonard, G. T., Bandyopadhyay, T., Stark, G. R. & Sen, G. C. Transcriptional induction by double-stranded RNA is mediated by interferon-stimulated response elements without activation of interferon-stimulated gene factor 3. J. Biol. Chem. 270, 19624–19629 (1995). (PMID: 764265010.1074/jbc.270.33.19624)
Diamond, M. S. & Farzan, M. The broad-spectrum antiviral functions of IFIT and IFITM proteins. Nat. Rev. Immunol. 13, 46–57 (2013). (PMID: 2323796410.1038/nri3344)
Fata-Hartley, C. L. & Palmenberg, A. C. Dipyridamole reversibly inhibits mengovirus RNA replication. J. Virol. 79, 11062–11070 (2005). (PMID: 16103157119357010.1128/JVI.79.17.11062-11070.2005)
Pulverer, J. E. et al. Temporal and spatial resolution of type I and III interferon responses in vivo. J. Virol. 84, 8626–8638 (2010). (PMID: 20573823291900210.1128/JVI.00303-10)
Whittemore, L. A. & Maniatis, T. Postinduction turnoff of beta-interferon gene expression. Mol. Cell Biol. 10, 1329–1337 (1990). (PMID: 2157136362234)
Chao, J. A., Patskovsky, Y., Almo, S. C. & Singer, R. H. Structural basis for the coevolution of a viral RNA-protein complex. Nat. Struct. Mol. Biol. 15, 103–105 (2008). (PMID: 1806608010.1038/nsmb1327)
Kamiyama, D. et al. Versatile protein tagging in cells with split fluorescent protein. Nat. Commun. 7, 11046 (2016). (PMID: 26988139480207410.1038/ncomms11046)
Albulescu, L., Wubbolts, R., van Kuppeveld, F. J. M. & Strating, J. R. P. M. Cholesterol shuttling is important for RNA replication of coxsackievirus B3 and encephalomyocarditis virus. Cell Microbiol. 17, 1144–1156 (2015). (PMID: 2564559510.1111/cmi.12425)
Belov, G. A. & van Kuppeveld, F. J. M. (+)RNA viruses rewire cellular pathways to build replication organelles. Curr. Opin. Virol. 2, 740–747 (2012). (PMID: 23036609710282110.1016/j.coviro.2012.09.006)
Feng, Q. et al. MDA5 detects the double-stranded RNA replicative form in picornavirus-infected cells. Cell Rep. 2, 1187–1196 (2012). (PMID: 23142662710398710.1016/j.celrep.2012.10.005)
Melia, C. E. et al. Escaping host factor PI4KB inhibition: enterovirus genomic RNA replication in the absence of replication organelles. Cell Rep. 21, 587–599 (2017). (PMID: 29045829565674510.1016/j.celrep.2017.09.068)
Schuster, S., Tholen, L. E., Overheul, G. J., van Kuppeveld, F. J. M. & van Rij, R. P. Deletion of cytoplasmic double-stranded RNA sensors does not uncover viral small interfering RNA production in human cells. mSphere 2, e00333-17 (2017). (PMID: 28815217555767810.1128/mSphere.00333-17)
Duke, G. M. & Palmenberg, A. C. Cloning and synthesis of infectious cardiovirus RNAs containing short, discrete poly(C) tracts. J. Virol. 63, 1822–1826 (1989). (PMID: 253866124846310.1128/jvi.63.4.1822-1826.1989)
Yan, X., Hoek, T. A., Vale, R. D. & Tanenbaum, M. E. Dynamics of translation of single mRNA molecules in vivo. Cell 165, 976–989 (2016). (PMID: 27153498488933410.1016/j.cell.2016.04.034)
Lyubimova, A. et al. Single-molecule mRNA detection and counting in mammalian tissue. Nat. Protoc. 8, 1743–1758 (2013). (PMID: 2394938010.1038/nprot.2013.109)
Gaspar, I., Wippich, F. & Ephrussi, A. Terminal deoxynucleotidyl transferase mediated production of labeled probes for single-molecule FISH or RNA capture. Bio Protoc. 8, e2750 (2018). (PMID: 3417927710.21769/BioProtoc.2750)
Stringer, C., Wang, T., Michaelos, M. & Pachitariu, M. Cellpose: a generalist algorithm for cellular segmentation. Nat. Methods 18, 100–106 (2021). (PMID: 3331865910.1038/s41592-020-01018-x)
Ulicna, K., Vallardi, G., Charras, G. & Lowe, A. R. Automated deep lineage tree analysis using a Bayesian single cell tracking approach. Front. Comput. Sci. 3, 734559 (2021). (PMID: 10.3389/fcomp.2021.734559)
Sardá-Espinosa, A. Time-series clustering in R using the dtwclust package. R J. https://doi.org/10.32614/RJ-2019-023 (2019). (PMID: 10.32614/RJ-2019-023)
المشرفين على المادة: 0 (Antiviral Agents)
تواريخ الأحداث: Date Created: 20231009 Date Completed: 20231108 Latest Revision: 20231122
رمز التحديث: 20231122
مُعرف محوري في PubMed: PMC10627821
DOI: 10.1038/s41564-023-01501-z
PMID: 37814072
قاعدة البيانات: MEDLINE
الوصف
تدمد:2058-5276
DOI:10.1038/s41564-023-01501-z