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Open Access 01-12-2013 | Methodology

A quantitative infection assay for human type I, II, and III interferon antiviral activities

Authors: Emily Voigt, Bahar İnankur, Ashley Baltes, John Yin

Published in: Virology Journal | Issue 1/2013

Abstract

Background

Upon virus infection, cells secrete a diverse group of antiviral molecules that signal proximal cells to enter into an antiviral state, slowing or preventing viral spread. These paracrine signaling molecules can work synergistically, so measurement of any one antiviral molecule does not reflect the total antiviral activity of the system.

Results

We have developed an antiviral assay based on replication inhibition of an engineered fluorescent vesicular stomatitis virus reporter strain on A549 human lung epithelial cells. Our assay provides a quantitative functional readout of human type I, II, and III interferon activities, and it provides better sensitivity, intra-, and inter-assay reproducibility than the traditional crystal violet based assay. Further, it eliminates cell fixation, rinsing, and staining steps, and is inexpensive to implement.

Conclusions

A dsRed2-strain of vesicular stomatitis virus that is sensitive to type I, II, and III interferons was used to develop a convenient and sensitive assay for interferon antiviral activity. We demonstrate use of the assay to quantify the kinetics of paracrine antiviral signaling from human prostate cancer (PC3) cells in response to viral infection. The assay is applicable to high-throughput screening for anti-viral compounds as well as basic studies of cellular antiviral signaling.

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Isaacs A, Lindenmann J: Virus interference. I. The interferon. Proc Roy Soc Lond Ser B 1957, 147: 258-267. 10.1098/rspb.1957.0048CrossRef

Kuri T, Habjan M, Penski N, Weber F: Species-independent bioassay for sensitive quantification of antiviral type I interferons. Virol J 2010, 7: 50. 10.1186/1743-422X-7-50PubMedPubMedCentralCrossRef

Kawaguchi S, Ishiguro Y, Imaizumi T, Mori F, Matsumiya T, Yoshida H, Ota K, Sakuraba H, Yamagata K, Sato Y, et al.: Retinoic acid-inducible gene-I is constitutively expressed and involved in IFN-gamma-stimulated CXCL9-11 production in intestinal epithelial cells. Immunol Lett 2009, 123: 9-13. 10.1016/j.imlet.2009.01.008PubMedCrossRef

Randall RE, Goodbourn S: Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 2008, 89: 1-47. 10.1099/vir.0.83391-0PubMedCrossRef

Ank N, West H, Bartholdy C, Eriksson K, Thomsen AR, Paludan SR: Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol 2006, 80: 4501-4509. 10.1128/JVI.80.9.4501-4509.2006PubMedPubMedCentralCrossRef

Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen ML, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP: IFN-lambda s mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 2003, 4: 69-77.PubMedCrossRef

Meager A, Visvalingam K, Dilger P, Bryan D, Wadhwa M: Biological activity of interleukins-28 and-29: Comparison with type I interferons. Cytokine 2005, 31: 109-118. 10.1016/j.cyto.2005.04.003PubMedCrossRef

Sheppard P, Kindsvogel W, Xu WF, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, et al.: IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 2003, 4: 63-68. 10.1038/ni873PubMedCrossRef

Zhou ZL, Hamming OJ, Ank N, Paludan SR, Nielsen AL, Hartmann R: Type III interferon (IFN) induces a type I IFN-like response in a restricted subset of cells through signaling pathways involving both the Jak-STAT pathway and the mitogen-activated protein kinases. J Virol 2007, 81: 7749-7758. 10.1128/JVI.02438-06PubMedPubMedCentralCrossRef

10.

Jewell NA, Cline T, Mertz SE, Smirnov SV, Flano E, Schindler C, Grieves JL, Durbin RK, Kotenko SV, Durbin JE: Lambda Interferon Is the Predominant Interferon Induced by Influenza A Virus Infection In Vivo. J Virol 2010, 84: 11515-11522. 10.1128/JVI.01703-09PubMedPubMedCentralCrossRef

11.

Khaitov MR, Laza-Stanca V, Edwards MR, Walton RP, Rohde G, Contoli M, Papi A, Stanciu LA, Kotenko SV, Johnston SL: Respiratory virus induction of alpha-, beta- and lambda-interferons in bronchial epithelial cells and peripheral blood mononuclear cells. Allergy 2009, 64: 375-386. 10.1111/j.1398-9995.2008.01826.xPubMedCrossRef

12.

Canosi U, Mascia M, Gazza L, SerlupiCrescenzi O, Donini S, Antonetti F, Galli G: A highly precise reporter gene bioassay for type I interferon. J Immunol Methods 1996, 199: 69-76. 10.1016/S0022-1759(96)00168-8PubMedCrossRef

13.

Seo YJ, Kim GH, Kwak HJ, Nam JS, Lee HJ, Suh SK, Baek KM, Sohn Y, Hong SH: Validation of a HeLa Mx2/Luc Reporter Cell Line for the Quantification of Human Type I Interferons. Pharmacol 2009, 84: 135-144. 10.1159/000235158CrossRef

14.

Kugel D, Pulverer JE, Koster M, Hauser H, Staeheli P: Novel Nonviral Bioassays for Mouse Type I and Type III Interferon. J Interferon Cytokine Res 2011, 31: 345-349. 10.1089/jir.2010.0079PubMedCrossRef

15.

Larocque L, Bliu A, Xu RR, Diress A, Wang JZ, Lin RT, He RT, Girard M, Li XG: Bioactivity Determination of Native and Variant Forms of Therapeutic Interferons. J Biomed Biotechnol 2011. Article ID 174615, 11 pages

16.

Burgi MD, Prieto C, Etcheverrigaray M, Kratje R, Oggero M, Bollati-Fogolin M: WISH cell line: From the antiviral system to a novel reporter gene assay to test the potency of human IFN-alpha and IFN-beta. J Immunol Methods 2012, 381: 70-74. 10.1016/j.jim.2012.04.010CrossRef

17.

Lewis JA: A Sensitive Biological Assay for Interferons. J Immunol Methods 1995, 185: 9-17. 10.1016/0022-1759(95)00100-OPubMedCrossRef

18.

Borderia AV, Hartmann BM, Fernandez-Sesma A, Moran TM, Sealfon SC: Antiviral-Activated Dendritic Cells: A Paracrine-Induced Response State. J Immunol 2008, 181: 6872-6881.PubMedCrossRef

19.

Miller-Jensen K, Janes KA, Brugge JS, Lauffenburger DA: Common effector processing mediates cell-specific responses to stimuli. Nat 2007, 448: 604-608. 10.1038/nature06001CrossRef

20.

Bauer AL, Beauchemin CAA, Perelson AS: Agent-based modeling of host-pathogen systems: The successes and challenges. Inform Sci 2009, 179: 1379-1389. 10.1016/j.ins.2008.11.012CrossRef

21.

Duca KA, Lam V, Keren I, Endler EE, Letchworth GJ, Novella IS, Yin J: Quantifying viral propagation in vitro: Toward a method for characterization of complex phenotypes. Biotechnol Prog 2001, 17: 1156-1165. 10.1021/bp010115mPubMedCrossRef

22.

Haseltine EL, Lam V, Yin J, Rawlings JB: Image-guided modeling of virus growth and spread. Bull Math Biol 2008, 70: 1730-1748. 10.1007/s11538-008-9316-3PubMedPubMedCentralCrossRef

23.

Howat TJ, Barreca C, O'Hare P, Gog JR, Grenfell BT: Modelling dynamics of the type I interferon response to in vitro viral infection. J R Soc Interface 2006, 3: 699-709. 10.1098/rsif.2006.0136PubMedPubMedCentralCrossRef

24.

Lam V, Duca KA, Yin J: Arrested spread of vesicular stomatitis virus infections in vitro depends on interferon-mediated antiviral activity. Biotechnol Bioeng 2005, 90: 793-804. 10.1002/bit.20467PubMedCrossRef

25.

Rubinstein S, Familletti PC, Pestka S: A convenient assay for interferons. J Virol 1981, 37: 755-758.PubMedPubMedCentral

26.

Berger Rentsch M, Zimmer G: A Vesicular Stomatitis Virus Replicon-Based Bioassay for the Rapid and Sensitive Determination of Multi-Species Type I Interferon. PLoS One 2011, 6: e25858. 10.1371/journal.pone.0025858PubMedPubMedCentralCrossRef

27.

Ahmed M, McKenzie MO, Puckett S, Hojnacki M, Poliquin L, Lyles DS: Ability of the matrix protein of vesicular stomatitis virus to suppress beta interferon gene expression is genetically correlated with the inhibition of host RNA and protein synthesis. J Virol 2003, 77: 4646-4657. 10.1128/JVI.77.8.4646-4657.2003PubMedPubMedCentralCrossRef

28.

Rentsch MB, Zimmer G: A Vesicular Stomatitis Virus Replicon-Based Bioassay for the Rapid and Sensitive Determination of Multi-Species Type I Interferon. PLoS One 2011,6(10):e25858. 10.1371/journal.pone.0025858CrossRef

29.

Dcunha J, Ramanujam S, Wagner RJ, Witt PL, Knight E, Borden EC: In vitro and in vivo secretion of human ISG15, an IFN-induced immunomodulatory cytokine. J Immunol 1996, 157: 4100-4108.

30.

Malakhova OA, Yan M, Malakhov MP, Yuan YZ, Ritchie KJ, Kim KI, Peterson LF, Shuai K, Zhang DE: Protein ISGylation modulates the JAK-STAT signaling pathway. Genes Dev 2003, 17: 455-460. 10.1101/gad.1056303PubMedPubMedCentralCrossRef

31.

Zhao C, Denison C, Huibregtse JM, Gygi S, Krug RM: Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proc Natl Acad Sci USA 2005, 102: 10200-10205. 10.1073/pnas.0504754102PubMedPubMedCentralCrossRef

32.

Bose S, Kar N, Maitra R, DiDonato JA, Banerjee AK: Temporal activation of NF-kappa B regulates an interferon-independent innate antiviral response against cytoplasmic RNA viruses. Proc Natl Acad Sci USA 2003, 100: 10890-10895. 10.1073/pnas.1832775100PubMedPubMedCentralCrossRef

33.

Muruve DA, Petrilli V, Zaiss AK, White LR, Clark SA, Ross PJ, Parks RJ, Tschopp J: The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nat 2008, 452: 103-107. 10.1038/nature06664CrossRef

34.

Poeck H, Bscheider M, Gross O, Finger K, Roth S, Rebsamen M, Hannesschlager N, Schlee M, Rothenfusser S, Barchet W, et al.: Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. Nat Immunol 2010, 11: 63-69. 10.1038/ni.1824PubMedCrossRef

35.

Buttmann M, Berberich-Siebelt F, Serfling E, Rieckmann P: Interferon-beta is a potent inducer of interferon regulatory factor-1/2-dependent IP-10/CXCL10 expression in primary human endothelial cells. J Vasc Res 2007, 44: 51-60. 10.1159/000097977PubMedCrossRef

36.

Hagele H, Allam R, Pawar RD, Reichel CA, Krombach F, Anders HJ: Double-Stranded DNA Activates Glomerular Endothelial Cells and Enhances Albumin Permeability via a Toll-Like Receptor-Independent Cytosolic DNA Recognition Pathway. Am J Pathol 2009, 175: 1896-1904. 10.2353/ajpath.2009.090182PubMedPubMedCentralCrossRef

37.

Kumar A, Zhang J, Yu FSX: Toll-like receptor 3 agonist poly(I:C)-induced antiviral response in human corneal epithelial cells. Immunol 2006, 117: 11-21. 10.1111/j.1365-2567.2005.02258.xCrossRef

38.

Kelly EJ, Nace R, Barber GN, Russell SJ: Attenuation of Vesicular Stomatitis Virus Encephalitis through MicroRNA Targeting. J Virol 2010, 84: 1550-1562. 10.1128/JVI.01788-09PubMedPubMedCentralCrossRef

39.

Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, Saib A, Voinnet O: A cellular microRNA mediates antiviral defense in human cells. Sci 2005, 308: 557-560. 10.1126/science.1108784CrossRef

40.

Mittelbrunn M, Sanchez-Madrid F: Intercellular communication: diverse structures for exchange of genetic information. Nat Rev Mol Cell Biol 2012, 13: 328-335.PubMedPubMedCentral

41.

Whelan SPJ, Ball LA, Barr JN, Wertz GTW: Efficient recovery of infectious Vesicular Stomatitis virus entirely from cDNA clones. Proc Natl Acad Sci USA 1995, 92: 8388-8392. 10.1073/pnas.92.18.8388PubMedPubMedCentralCrossRef

42.

Lawson ND, Stillman EA, Whitt MA, Rose JK: Recombinant Vesicular Stomatitis Virus from DNA. Proc Natl Acad Sci USA 1995, 92: 4477-4481. 10.1073/pnas.92.10.4477PubMedPubMedCentralCrossRef

43.

Grdzelishvili VZ, Smallwood S, Tower D, Hall RL, Hunt DM, Moyer SA: Identification of a new region in the vesicular stomatitis virus L polymerase protein which is essential for mRNA cap methylation. Virol 2006, 350: 394-405. 10.1016/j.virol.2006.02.021CrossRef

44.

Das SC, Nayak D, Zhou Y, Pattnaik AK: Visualization of intracellular transport of vesicular stomatitis virus nucleocapsids in living cells. J Virol 2006, 80: 6368-6377. 10.1128/JVI.00211-06PubMedPubMedCentralCrossRef

45.

Ferran MC, LucasLenard JM: The vesicular stomatitis virus matrix protein inhibits transcription from the human beta interferon promoter. J Virol 1997, 71: 371-377.PubMedPubMedCentral

46.

Ahmed M, Lyles DS: Effect of vesicular stomatitis virus matrix protein on transcription directed by host RNA polymerases I, II, and III. J Virol 1998, 72: 8413-8419.PubMedPubMedCentral

47.

Fuerst TR, Niles EG, Studier FW, Moss B: Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci USA 1986, 83: 8122-8126. 10.1073/pnas.83.21.8122PubMedPubMedCentralCrossRef

Title: A quantitative infection assay for human type I, II, and III interferon antiviral activities
Authors: Emily Voigt
Bahar İnankur
Ashley Baltes
John Yin
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Virology Journal / Issue 1/2013
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/1743-422X-10-224

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Abstract

Background

Results

Conclusions

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