[en] OBJECTIVE: To determine the contribution of MX dynamin, oligoadenylate synthetase (OAS), and double-stranded RNA-dependent protein kinase R (PKR) to the antiviral effects of type 1 interferons (IFNs) against bovine parainfluenza-3 virus (PI-3V) infection of Vero cells. SAMPLE POPULATION: Vero cell cultures. PROCEDURES: PI-3V yield was first compared between control and transfected type 1 IFNs-incompetent Vero cells expressing recombinant OAS or MX proteins. Afterwards, phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha) was used to scale the degree of PKR activation upon infection of Vero cells by PI-3V. RESULTS: Overexpression of OAS did not result in significantly decreased viral replication. Phosphorylated eIF2alpha forms, the hallmark of PKR activation, were not increased in IFNalpha-primed infected Vero cells. Although human MXA contributed to partial blockade of replication of bovine PI-3V, the antiviral effect was not as strong as that of IFNalpha. CONCLUSIONS AND CLINICAL RELEVANCE: The powerful anti-Paramyxovirus activity of type 1 IFNs is mediated by noncanonic pathways.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Leroy, M.
Baise, Etienne ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques
Pire, G.
Desmecht, Daniel ; Université de Liège - ULiège > Département de morphologie et pathologie > Pathologie spéciale et autopsies
Language :
English
Title :
Contribution of MX dynamin, oligoadenylate synthetase, and protein kinase R to anti-paramyxovirus activity of type-1 interferons in vitro
Publication date :
2007
Journal title :
American Journal of Veterinary Research
ISSN :
0002-9645
eISSN :
1943-5681
Publisher :
American Veterinary Medical Association, Schaumburg, United States - Illinois
Bryson DG, McNulty MS, Ball HJ, et al. The experimental production of pneumonia in calves by intranasal inoculation of parainfluenza type III virus. Vet Rec 1979;105:566-573.
Graham DA, McShane J, Mawhinney KA, et al. Evaluation of a single dilution ELISA system for detection of seroconversion to bovine viral diarrhea virus, bovine respiratory syncytial virus, parainfluenza-3 virus, and infectious bovine rhinotracheitis virus: comparison with testing by virus neutralization and hemagglutination inhibition. J Vet Diagn Invest 1998;10:43-48.
Lengyel P. Tumor-suppressor genes: news about the interferon connection. Proc Natl Acad Sci USA 1993;90:5893-5895.
Mrkic B, Pavlovic J, Rulicke T, et al. Measles virus spread and pathogenesis in genetically modified mice. J Virol 1998;72:7420-7427.
Pestka S, Langer JA, Zoon KC, et al. Interferons and their actions. Annu Rev Biochem 1987;56:727-777.
Haller O, Frese M, Kochs G. Mx proteins: mediators of innate resistance to RNA viruses. Rev Sci Tech 1998;17:220-230.
Katze MG, Wambach M, Wong ML, et al. Functional expression and RNA binding analysis of the interferon-induced, double-stranded RNA-activated, 68,000-Mr protein kinase in a cell-free system. Mol Cell Biol 1991;11:5497-5505.
Foster GR. Interferons in host defense. Semin Liver Dis 1997;17:287-295.
Lee SH, Vidal SM. Functional diversity of Mx proteins: variations on a theme of host resistance to infection. Genome Res 2002;12:527-530.
Clemens MJ, Elia A. The double-stranded RNA-dependent protein kinase PKR: structure and function. J Interferon Cytokine Res 1997;17:503-524.
Khabar KS, Dhalla M, Siddiqui Y, et al. Effect of deficiency of the double-stranded RNA-dependent protein kinase, PKR, on antiviral resistance in the presence or absence of ribonuclease 1: HSV-1 replication is particularly sensitive to deficiency of the major IFN-mediated enzymes. J Interferon Cytokine Res 2000;20:653-659.
Chinsangaram J, Koster M, Grubman MJ. Inhibition of L-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded RNA-dependent protein kinase. J Virol 2001;75:5498-5503.
Stojdl DF, Abraham N, Knowles S, et al. The murine double-stranded RNA-dependent protein kinase PKR is required for resistance to vesicular stomatitis virus. J Virol 2000;74:9580-9585.
Muto NF, Martinand-Mari C, Adelson ME, et al. Inhibition of replication of reactivated human immunodeficiency virus type 1 (HIV-1) in latently infected U1 cells transduced with an HIV-1 long terminal repeat-driven PKR cDNA construct. J Virol 1999;73:9021-9028.
Stewart MJ, Blum MA, Sherry B. PKR's protective role in viral myocarditis. Virology 2003;314:92-100.
Kerr IM, Brown RE. pppa2′p5′a2′p5′a: an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells. Proc Natl Acad Sci U S A 1978; 75:256-260.
Silverman RH. 2-5 a-dependent RNase 1: a regulated endoribonuclease in the interferon syste. In: D'Alessio G, Riordan JF, eds. Ribonucleases: structure and function. New York: Academic Press Inc, 1997;515-551.
Carr DJ, Al-Khatib K, James CM, et al. Interferon-beta suppresses herpes simplex virus type 1 replication in trigeminal ganglion cells through an RNase 1-dependent pathway. J Neuroimmunol 2003;14:40-46.
Lucas M, Mashimo T, Frenkiel MP, et al. Infection of mouse neurones by West Nile virus is modulated by the interferon-inducible 2′-5′ oligoadenylate synthetase 1b protein. Immunol Cell Biol 2003;81:230-236.
Li XL, Blackford JA, Hassel BA. RNase 1 mediates the antiviral effect of interferon through a selective reduction in viral RNA during encephalomyocarditis virus infection. J Virol 1998;72:2752-2759.
Zheng X, Silverman RH, Zhou A, et al. Increased severity of HSV-1 keratitis and mortality in mice lacking the 2-5a-dependent RNase 1 gene. Invest Ophthalmol Vis Sci 2001;42:120-126.
Choudhary S, Gao J, Leaman DW, et al. Interferon action against human parainfluenza virus type 3: involvement of a novel antiviral pathway in the inhibition of transcription. J Virol 2001;75:4823-4831.
Zhao H, De BP, Das T, et al. Inhibition of human parainfluenza virus-3 replication by interferon and human MxA. Virology 1996; 220:330-338.
Fulton RW, Downing MM, Cummins JM. Antiviral effects of bovine interferons on bovine respiratory tract viruses. J Clin Microbiol 1984;19:492-497.
Gillespie JH, Robson DS, Scott FW, et al. In vitro protective effect of bacteria-derived bovine alpha interferon against selected bovine viruses. J Clin Microbiol 1985;22:912-914.
Atreya PL, Kulkarni S. Respiratory syncytial virus strain A2 is resistant to the antiviral effects of type 1 interferons and human MxA. Virology 1999;261:227-241.
Koumenis C, Naczki C, Koritzinsky M, et al. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eif2alpha. Mol Cell Biol 2002;22:7405-7416.
Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev 2001;14:778-809.
Rebouillat D, Hovanessian AG. The human 2′,5′-oligoadenylate synthetase family: interferon-induced proteins with unique enzymatic properties. J Interferon Cytokine Res 1999;19:295-308.
Chebath J, Benech P, Revel M, et al. Constitutive expression of (2′-5′) oligo A synthetase confers resistance to Picornavirus infection. Nature 1987;330:587-588.
Sangster MY, Urosevic N, Mansfield JP, et al. Mapping the Flv locus controlling resistance to flaviviruses on mouse chromosome 5. J Virol 1994;68:448-452.
Ghosh A, Sarkar SN, Sen GC. Cell growth regulatory and antiviral effects of the p69 isozyme of 2-5 (A) synthetase. Virology 2000;266:319-328.
Frese M, Kochs G, Meier-Dieter U, et al. Human Mxa protein inhibits tick-borne Thogoto virus but not Dhori virus. J Virol 1995;69:3904-3909.
Frese M, Kochs G, Feldmann H, et al. Inhibition of Bunyaviruses, Phleboviruses, and Hantaviruses by human Mxa protein. J Virol 1996;70:915-923.
Schwemmle M, Weining KC, Richter MF, et al. Vesicular stomatitis virus transcription inhibited by purified Mxa protein. Virology 1995;206:545-554.
Landis H, Simon-Jodicke A, Kloti A, et al. Human MxA protein confers resistance to Semliki forest virus and inhibits the amplification of a Semliki forest virus-based replicon in the absence of viral structural proteins. J Virol 1998;72:1516-1522.
Chieux V, Chehadeh W, Harvey J, et al. Inhibition of Coxsackie virus B4 replication in stably transfected cells expressing human Mxa protein. Virology 2001;283:84-92.
Gordien E, Rosmorduc O, Peltekian C, et al. Inhibition of hepatitis B virus replication by the interferon-inducible MxA protein. J Virol 2001;75:2684-2691.
Leroy M, Baise E, Pire G, et al. Resistance of Paramyxoviridae to type I interferon-induced Bos taurus Mx1 dynamin. J Interferon Cytokine Res 2005;25:192-201.
Benkirane M, Neuveut C, Chun RF, et al. Oncogenic potential of tar RNA binding protein TRBP and its regulatory interaction with RNA-dependent protein kinase PKR. EMBO J 1997;16:611-624.
Abraham N, Stojdl DE Duncan PI, et al. Characterization of transgenic mice with targeted disruption of the catalytic domain of the double-stranded RNA-dependent protein kinase, PKR. J Biol Chem 1999;274:5953-5962.
Balachandran S, Roberts PC, Brown LE, et al. Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection. Immunity 2000;13:129-141.
Mathews MB, Shenk T. Adenovirus-associated RNA and translational control. J Virol 1991;65:5657-5662.
Meurs EF, Watanabe Y, Kadereit S, et al. Constitutive expression of human double-stranded RNA-activated p68 kinase in murine cells mediates phosphorylation of eukaryotic initiation factor 2 and partial resistance to encephalomyocarditis virus growth. J Virol 1992;66:5805-5814.
Brand SR, Kobayashi R, Mathews MB. The TAT protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR. J Biol Chem 1997;272:8388-8395.
Yang YL, Reis LF, Pavlovic J, et al. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J 1995;14:6095-6106.
Lu Y, Wambach M, Katze MG, et al. Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elf-2 translation initiation factor. Virology 1995;214:222-228.
Patterson JB, SamueL CE. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Mol Cell Biol 1995;15:5376-5388.
Nguyen LH, Espert L, Mechti N, et al. The human interferon- and estrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro. Biochemistry 2001;40:74-79.
Yuan W, Krug RM. Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. EMBO J 2001;20:362-371.