Interferon-inducible antiviral effectors
TLDR
This Review discusses four main effector pathways of the IFN-mediated antiviral response: the Mx GTPase pathway, the 2′,5′-oligoadenylate-synthetase-directed ribonuclease L pathways, the protein kinase R pathway and the ISG15 ubiquitin-like pathway.Abstract:
Since the discovery of interferons (IFNs), considerable progress has been made in describing the nature of the cytokines themselves, the signalling components that direct the cell response and their antiviral activities. Gene targeting studies have distinguished four main effector pathways of the IFN-mediated antiviral response: the Mx GTPase pathway, the 2',5'-oligoadenylate-synthetase-directed ribonuclease L pathway, the protein kinase R pathway and the ISG15 ubiquitin-like pathway. As discussed in this Review, these effector pathways individually block viral transcription, degrade viral RNA, inhibit translation and modify protein function to control all steps of viral replication. Ongoing research continues to expose additional activities for these effector proteins and has revealed unanticipated functions of the antiviral response.read more
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Thomson,Alfred A.R. Thompson,Ryan S Thwaites,L Turtle,Maria Zambon,Hayley Hardwick,Chloe Donohue,Ronan A Lyons,Lisa Norman,Riinu Pius,Thomas M Drake,Cameron J Fairfield,Stephen R Knight,Kenneth A. McLean,Derek Murphy,C. A. Shaw,Jo Dalton,Michelle Girvan,Egle Saviciute,Stuart K. Roberts,Janet Harrison,Laura Marsh,Marie Connor,Sophie Halpin,Carrol Gamble,Gary Leeming,Murray Wham,William Greenhalf,V. Shaw,Sarah D. McDonald,Andrea Ganna,Patrick Sulem,D A van Heel,M. Cordioli,Gardar Sveinbjornsson,M. E. K. Niemi,Janie F. Shelton,A. J. Shastri,C. Ye,C. H. Weldon,T. Filshtein-Sonmez,D. Coker,A. Symons,J. Esparza-Gordillo,Stella Aslibekyan,Adam Auton,J. E. Krieger,E. Marques,C. E. Jannes,Francesca Mari,S. Daga,Margherita Baldassarri,Elisa Benetti,Simone Furini,Chiara Fallerini,Francesca Fava,Floriana Valentino,G. Doddato,Annarita Giliberti,Rossella Tita,Sara Amitrano,Mirella Bruttini,S. Croci,I. Meloni,A. M. Pinto,E. Frullanti,Maria Antonietta Mencarelli,C. L. Rizzo,Francesca Montagnani,L. Di Sarno,A. Tommasi,Marta Palmieri,Arianna Emiliozzi,M. Fabbiani,Barbara Rossetti,Giacomo Zanelli,Elena Bargagli,Laura Bergantini,Miriana d'Alessandro,Paolo Cameli,D. Bennet,Federico Anedda,Simona Marcantonio,Sabino Scolletta,Federico Franchi,Maria Antonietta Mazzei,S. Guerrini,Edoardo Conticini,Luca Cantarini,Bruno Frediani,D. Tacconi,C. Spertilli,M. Feri,Abele Donati,R. Scala,L. Guidelli,G. Spargi,M. Corridi,C. Nencioni,L. Croci,G. P. Caldarelli,M. Spagnesi,P. Piacentini,M. Bandini,E. Desanctis,S. Cappelli,A. Canaccini,A. Verzuri,V. Anemoli,A. Ognibene,M. Vaghi,A d'Arminio Monforte,Esther Merlini,M. U. Mondelli,S. Mantovani,S. Ludovisi,Massimo Girardis,S. Venturelli,M. Sita,Andrea Cossarizza,A. Antinori,Alessandra Vergori,Stefano Rusconi,M. Siano,A. Gabrieli,Agostino Riva,Daniela Francisci,Elisabetta Schiaroli,P. G. Scotton,F. Andretta,S. Panese,R. Scaggiante,F. Gatti,S. G. Parisi,Francesco Castelli,M. E. Quiros-Roldan,P. Magro,Isabella Zanella,M. Della Monica,Carmelo Piscopo,Mario Capasso,Roberta Russo,Immacolata Andolfo,Achille Iolascon,G. Fiorentino,M. Carella,Marco Castori,Giuseppe Merla,Filippo Aucella,P. Raggi,C. Marciano,R. Perna,Matteo Bassetti,A. Di Biagio,M. Sanguinetti,L. Masucci,Serafina Valente,Marco Mandalà,A. Giorli,L. Salerni,P. Zucchi,P. Parravicini,E. Menatti,S. Baratti,T. Trotta,F. Giannattasio,G. Coiro,F. Lena,D. A. Coviello,Cristina Mussini,G. Bosio,E. Martinelli,Sandro Mancarella,L. Tavecchia,L. Crotti,N. Picchiotti,M. Gori,C. Gabbi,M. Sanarico,S. Ceri,P. Pinoli,F. Raimondi,F. Biscarini,A. Stella,Xia Shen,Xia Shen,Chris P. Ponting,Angie Fawkes,Albert Tenesa,Albert Tenesa,Mark J. Caulfield,Richard H Scott,K Rowan,Lee Murphy,Peter J. M. Openshaw,Peter J. M. Openshaw,Malcolm G Semple,Veronique Vitart,James F. Wilson +1449 more
TL;DR: The GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2244 critically ill Covid-19 patients from 208 UK intensive care units is reported, finding evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease.
Journal ArticleDOI
Innate immunity to influenza virus infection.
Akiko Iwasaki,Padmini S. Pillai +1 more
TL;DR: Whether the outcome of innate sensor stimulation promotes antiviral resistance or disease tolerance, and proposed rational treatment strategies for the acute respiratory disease that is caused by influenza virus infection are considered.
Journal ArticleDOI
Autophagy, Immunity, and Microbial Adaptations
Vojo Deretic,Beth Levine +1 more
TL;DR: The ability of eukaryotic pathogens to deploy their own autophagic machinery may also contribute to microbial pathogenesis, and a complex interplay between Autophagy and microbial adaptations against autophagy governs the net outcome of host-microbe encounters.
References
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Virus interference. I The interferon
Alick Isaacs,Jean Lindenmann +1 more
TL;DR: During a study of the interference produced by heat-inactivated influenza virus with the growth of live virus in fragments of chick chorio-allantoic membrane it was found that following incubation of heated virus with membrane a new factor was released.
Journal ArticleDOI
Functional role of type I and type II interferons in antiviral defense.
Ulrike Müller,Ulrich Steinhoff,Luiz F. L. Reis,Silvio Hemmi,Jovan Pavlovic,Rolf M. Zinkernagel,Michel Aguet +6 more
TL;DR: Comparison of mice lacking either type I or type II IFN receptors showed that, at least in response to some viruses, both IFN systems are essential for antiviral defense and are functionally nonredundant.
Journal ArticleDOI
Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays
TL;DR: The results demonstrate the usefulness of oligonucleotide arrays in monitoring mammalian gene expression on a broad and unprecedented scale and provide insights into the basic mechanisms of IFN actions.
Journal ArticleDOI
Interferons at age 50: past, current and future impact on biomedicine.
Ernest C. Borden,Ganes C. Sen,Gilles Uzé,Robert H. Silverman,Richard M. Ransohoff,Graham R. Foster,George Stark Stark +6 more
TL;DR: The goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential.
Journal ArticleDOI
Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon.
Eliane F. Meurs,Karen Chong,Julien Galabru,N.Shaun B. Thomas,Ian M. Kerr,Bryan R.G. Williams,Bryan R.G. Williams,Ara G. Hovanessian +7 more
TL;DR: The molecular cloning and characterization of several related cDNAs from which can be deduced the full-length p68 kinase sequence are reported, which predicts a protein of 550 amino acids containing all of the conserved domains specific for members of the protein kinase family.