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Published Online: 8 December 2011

Intranasal Delivery of an Adjuvanted Modified Live Porcine Reproductive and Respiratory Syndrome Virus Vaccine Reduces ROS Production

Publication: Viral Immunology
Volume 24, Issue Number 6

Abstract

Reactive oxygen species (ROS) are produced predominantly by phagocytic cells in response to microbial infections. When produced at optimal levels ROS have potent antimicrobial properties. However, excessive production of ROS induces apoptosis/necrosis of infected as well as bystander cells, resulting in inflammatory pathology. Previously we showed that vaccination of pigs with a modified live porcine reproductive and respiratory syndrome virus vaccine (PRRS-MLV) administered intranasally with a potent mucosal adjuvant M. tuberculosis whole-cell lysate (Mtb WCL) induces protective immunity against PRRSV challenge. In this study, using bronchoalveolar lavage fluid cells and peripheral blood mononuclear cells harvested from that study were quantified for the levels of ROS produced. Our results indicated that in vaccinated pigs, levels of ROS were lower compared to unvaccinated PRRSV-challenged pigs. In unvaccinated but PRRSV-challenged pigs, the higher ROS production was associated with increased inflammatory lung pathology. In conclusion, our results suggest that intranasal immunization using PRRS-MLV along with a potent mucosal adjuvant protects pigs against both homologous and virulent heterologous PRRSV challenge, which was associated with reduced ROS production and reduced lung pathology compared to control virus-challenged pigs.

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References

1.
Wang XEaton MMayer M et al. Porcine reproductive and respiratory syndrome virus productively infects monocyte-derived dendritic cells and compromises their antigen-presenting abilityArch Virol2007152289-303. 1. Wang X, Eaton M, Mayer M, et al.: Porcine reproductive and respiratory syndrome virus productively infects monocyte-derived dendritic cells and compromises their antigen-presenting ability. Arch Virol 2007;152:289–303.
2.
Xiao ZBatista LDee S et al. The level of virus-specific T-cell and macrophage recruitment in porcine reproductive and respiratory syndrome virus infection in pigs is independent of virus loadJ Virol2004785923-5933. 2. Xiao Z, Batista L, Dee S, et al.: The level of virus-specific T-cell and macrophage recruitment in porcine reproductive and respiratory syndrome virus infection in pigs is independent of virus load. J Virol 2004;78:5923–5933.
3.
Albina ECarrat CCharley B. Interferon-alpha response to swine arterivirus (PoAV), the porcine reproductive and respiratory syndrome virusJ Interferon Cytokine Res199818485-490. 3. Albina E, Carrat C, and Charley B: Interferon-alpha response to swine arterivirus (PoAV), the porcine reproductive and respiratory syndrome virus. J Interferon Cytokine Res 1998;18:485–490.
4.
Renukaradhya GJAlekseev KJung K et al. Porcine reproductive and respiratory syndrome virus-induced immunosuppression exacerbates the inflammatory response to porcine respiratory coronavirus in pigsViral Immunol201023457-466. 4. Renukaradhya GJ, Alekseev K, Jung K, et al.: Porcine reproductive and respiratory syndrome virus-induced immunosuppression exacerbates the inflammatory response to porcine respiratory coronavirus in pigs. Viral Immunol 2010;23:457–466.
5.
Sirinarumitr TZhang YKluge JP et al. A pneumo-virulent United States isolate of porcine reproductive and respiratory syndrome virus induces apoptosis in bystander cells both in vitro and in vivoJ Gen Virol199879Pt 122989-2995. 5. Sirinarumitr T, Zhang Y, Kluge JP, et al.: A pneumo-virulent United States isolate of porcine reproductive and respiratory syndrome virus induces apoptosis in bystander cells both in vitro and in vivo. J Gen Virol 1998;79(Pt 12):2989–2995.
6.
Xiao SMo DWang Q et al. Aberrant host immune response induced by highly virulent PRRSV identified by digital gene expression tag profilingBMC Genomics201011544. 6. Xiao S, Mo D, Wang Q, et al.: Aberrant host immune response induced by highly virulent PRRSV identified by digital gene expression tag profiling. BMC Genomics 2010;11:544.
7.
Chvanov MPetersen OHTepikin A. Free radicals and the pancreatic acinar cells: role in physiology and pathologyPhilos Trans R Soc Lond B Biol Sci20053602273-2284. 7. Chvanov M, Petersen OH, and Tepikin A: Free radicals and the pancreatic acinar cells: role in physiology and pathology. Philos Trans R Soc Lond B Biol Sci 2005;360:2273–2284.
8.
Quinn MTGauss KA. Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidasesJ Leukoc Biol200476760-781. 8. Quinn MT, and Gauss KA: Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases. J Leukoc Biol 2004;76:760–781.
9.
Droge W. Free radicals in the physiological control of cell functionPhysiol Rev20028247-95. 9. Droge W: Free radicals in the physiological control of cell function. Physiol Rev 2002;82:47–95.
10.
Green DRReed JC. Mitochondria and apoptosisScience19982811309-1312. 10. Green DR, and Reed JC: Mitochondria and apoptosis. Science 1998;281:1309–1312.
11.
Donko APeterfi ZSum A et al. Dual oxidasesPhilos Trans R Soc Lond B Biol Sci20053602301-2308. 11. Donko A, Peterfi Z, Sum A, et al.: Dual oxidases. Philos Trans R Soc Lond B Biol Sci 2005;360:2301–2308.
12.
Suarez PDiaz-Guerra MPrieto C et al. Open reading frame 5 of porcine reproductive and respiratory syndrome virus as a cause of virus-induced apoptosisJ Virol1996702876-2882. 12. Suarez P, Diaz-Guerra M, Prieto C, et al.: Open reading frame 5 of porcine reproductive and respiratory syndrome virus as a cause of virus-induced apoptosis. J Virol 1996;70:2876–2882.
13.
Fang FC. Antimicrobial reactive oxygen and nitrogen species: concepts and controversiesNat Rev Microbiol20042820-832. 13. Fang FC: Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat Rev Microbiol 2004;2:820–832.
14.
Steiner JHaughey NLi W et al. Oxidative stress and therapeutic approaches in HIV dementiaAntioxid Redox Signal200682089-2100. 14. Steiner J, Haughey N, Li W, et al.: Oxidative stress and therapeutic approaches in HIV dementia. Antioxid Redox Signal 2006;8:2089–2100.
15.
Wang TWeinman SA. Causes and consequences of mitochondrial reactive oxygen species generation in hepatitis CJ Gastroenterol Hepatol200621Suppl 3S34-S37. 15. Wang T, and Weinman SA: Causes and consequences of mitochondrial reactive oxygen species generation in hepatitis C. J Gastroenterol Hepatol 2006;21(Suppl 3):S34–S37.
16.
Akaike TNoguchi YIjiri S et al. Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicalsProc Natl Acad Sci USA1996932448-2453. 16. Akaike T, Noguchi Y, Ijiri S, et al.: Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. Proc Natl Acad Sci USA 1996;93:2448–2453.
17.
Kash JCBasler CFGarcia-Sastre A et al. Global host immune response: pathogenesis and transcriptional profiling of type A influenza viruses expressing the hemagglutinin and neuraminidase genes from the 1918 pandemic virusJ Virol2004789499-9511. 17. Kash JC, Basler CF, Garcia-Sastre A, et al.: Global host immune response: pathogenesis and transcriptional profiling of type A influenza viruses expressing the hemagglutinin and neuraminidase genes from the 1918 pandemic virus. J Virol 2004;78:9499–9511.
18.
White MRCrouch EVesona J et al. Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virusAm J Physiol Lung Cell Mol Physiol2005289L606-L616. 18. White MR, Crouch E, Vesona J, et al.: Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus. Am J Physiol Lung Cell Mol Physiol 2005;289:L606–L616.
19.
Davis ICZajac AJNolte KB et al. Elevated generation of reactive oxygen/nitrogen species in hantavirus cardiopulmonary syndromeJ Virol2002768347-8359. 19. Davis IC, Zajac AJ, Nolte KB, et al.: Elevated generation of reactive oxygen/nitrogen species in hantavirus cardiopulmonary syndrome. J Virol 2002;76:8347–8359.
20.
Adler HBeland JLDel-Pan NC et al. Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2)J Exp Med19971851533-1540. 20. Adler H, Beland JL, Del-Pan NC, et al.: Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2). J Exp Med 1997;185:1533–1540.
21.
Kim WILee DSJohnson W et al. Effect of genotypic and biotypic differences among PRRS viruses on the serologic assessment of pigs for virus infectionVet Microbiol20071231-14. 21. Kim WI, Lee DS, Johnson W, et al.: Effect of genotypic and biotypic differences among PRRS viruses on the serologic assessment of pigs for virus infection. Vet Microbiol 2007;123:1–14.
22.
VanCott JLBrim TASimkins RASaif LJ. Isotype-specific antibody-secreting cells to transmissible gastroenteritis virus and porcine respiratory coronavirus in gut- and bronchus-associated lymphoid tissues of suckling pigsJ Immunol19931503990-4000. 22. VanCott JL, Brim TA, Simkins RA, and Saif LJ: Isotype-specific antibody-secreting cells to transmissible gastroenteritis virus and porcine respiratory coronavirus in gut- and bronchus-associated lymphoid tissues of suckling pigs. J Immunol 1993;150:3990–4000.
23.
Loving CLBrockmeier SLSacco RE. Differential type I interferon activation and susceptibility of dendritic cell populations to porcine arterivirusImmunology2007120217-229. 23. Loving CL, Brockmeier SL, and Sacco RE: Differential type I interferon activation and susceptibility of dendritic cell populations to porcine arterivirus. Immunology 2007;120:217–229.
24.
Tunc OThompson JTremellen K. Development of the NBT assay as a marker of sperm oxidative stressInt J Androl20103313-21. 24. Tunc O, Thompson J, and Tremellen K: Development of the NBT assay as a marker of sperm oxidative stress. Int J Androl 2010;33:13–21.
25.
Choi HSKim JWCha YNKim C. A quantitative nitroblue tetrazolium assay for determining intracellular superoxide anion production in phagocytic cellsJ Immunoassay Immunochem20062731-44. 25. Choi HS, Kim JW, Cha YN, and Kim C: A quantitative nitroblue tetrazolium assay for determining intracellular superoxide anion production in phagocytic cells. J Immunoassay Immunochem 2006;27:31–44.
26.
Li YTrush MA. Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species productionBiochem Biophys Res Commun1998253295-299. 26. Li Y, and Trush MA: Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production. Biochem Biophys Res Commun 1998;253:295–299.
27.
Lambert AJBuckingham JABoysen HMBrand MD. Diphenyleneiodonium acutely inhibits reactive oxygen species production by mitochondrial complex I during reverse, but not forward electron transportBiochim Biophys Acta20081777397-403. 27. Lambert AJ, Buckingham JA, Boysen HM, and Brand MD: Diphenyleneiodonium acutely inhibits reactive oxygen species production by mitochondrial complex I during reverse, but not forward electron transport. Biochim Biophys Acta 2008;1777:397–403.
28.
Fattorossi ANisini RLe Moli S et al. Flow cytometric evaluation of nitro blue tetrazolium (NBT) reduction in human polymorphonuclear leukocytesCytometry199011907-912. 28. Fattorossi A, Nisini R, Le Moli S, et al.: Flow cytometric evaluation of nitro blue tetrazolium (NBT) reduction in human polymorphonuclear leukocytes. Cytometry 1990;11:907–912.
29.
Schmalstieg FCRudloff HEAnderson DC. Binding of the adhesive protein complex (LFA-1/Mac-1/p150,95) to concanavalin AJ Leukoc Biol198639193-203. 29. Schmalstieg FC, Rudloff HE, and Anderson DC: Binding of the adhesive protein complex (LFA-1/Mac-1/p150,95) to concanavalin A. J Leukoc Biol 1986;39:193–203.
30.
McPhail LCHenson PMJohnston RB Jr. Respiratory burst enzyme in human neutrophils. Evidence for multiple mechanisms of activationJ Clin Invest198167710-716. 30. McPhail LC, Henson PM, and Johnston RB Jr: Respiratory burst enzyme in human neutrophils. Evidence for multiple mechanisms of activation. J Clin Invest 1981;67:710–716.
31.
Dwivedi VManickam CPatterson R et al. Cross-protective immunity to porcine reproductive and respiratory syndrome virus by intranasal delivery of a live virus vaccine with a potent adjuvantVaccine2011294058-4066. 31. Dwivedi V, Manickam C, Patterson R, et al.: Cross-protective immunity to porcine reproductive and respiratory syndrome virus by intranasal delivery of a live virus vaccine with a potent adjuvant. Vaccine 2011;29:4058–4066.
32.
Chiou MTJeng CRChueh LL et al. Effects of porcine reproductive and respiratory syndrome virus (isolate tw91) on porcine alveolar macrophages in vitroVet Microbiol2000719-25. 32. Chiou MT, Jeng CR, Chueh LL, et al.: Effects of porcine reproductive and respiratory syndrome virus (isolate tw91) on porcine alveolar macrophages in vitro. Vet Microbiol 2000;71:9–25.
33.
Jung KRenukaradhya GJAlekseev KP et al. Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infectionsJ Gen Virol2009902713-2723. 33. Jung K, Renukaradhya GJ, Alekseev KP, et al.: Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections. J Gen Virol 2009;90:2713–2723.
34.
Lee SMKleiboeker SB. Porcine reproductive and respiratory syndrome virus induces apoptosis through a mitochondria-mediated pathwayVirology2007365419-434. 34. Lee SM, and Kleiboeker SB: Porcine reproductive and respiratory syndrome virus induces apoptosis through a mitochondria-mediated pathway. Virology 2007;365:419–434.
35.
Nathan CShiloh MU. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogensProc Natl Acad Sci USA2000978841-8848. 35. Nathan C, and Shiloh MU: Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci USA 2000;97:8841–8848.
36.
Elloumi HZHolland SM. Diagnostic assays for chronic granulomatous disease and other neutrophil disordersMethods Mol Biol2007412505-523. 36. Elloumi HZ, and Holland SM: Diagnostic assays for chronic granulomatous disease and other neutrophil disorders. Methods Mol Biol 2007;412:505–523.
37.
Vowells SJSekhsaria SMalech HL et al. Flow cytometric analysis of the granulocyte respiratory burst: a comparison study of fluorescent probesJ Immunol Methods199517889-97. 37. Vowells SJ, Sekhsaria S, Malech HL, et al.: Flow cytometric analysis of the granulocyte respiratory burst: a comparison study of fluorescent probes. J Immunol Methods 1995;178:89–97.
38.
Acker H. The oxygen sensing signal cascade under the influence of reactive oxygen speciesPhilos Trans R Soc Lond B Biol Sci20053602201-2210. 38. Acker H: The oxygen sensing signal cascade under the influence of reactive oxygen species. Philos Trans R Soc Lond B Biol Sci 2005;360:2201–2210.
39.
Martin JHEdwards SW. Changes in mechanisms of monocyte/macrophage-mediated cytotoxicity during culture. Reactive oxygen intermediates are involved in monocyte-mediated cytotoxicity, whereas reactive nitrogen intermediates are employed by macrophages in tumor cell killingJ Immunol19931503478-3486. 39. Martin JH, and Edwards SW: Changes in mechanisms of monocyte/macrophage-mediated cytotoxicity during culture. Reactive oxygen intermediates are involved in monocyte-mediated cytotoxicity, whereas reactive nitrogen intermediates are employed by macrophages in tumor cell killing. J Immunol 1993;150:3478–3486.
40.
Clutton S. The importance of oxidative stress in apoptosisBr Med Bull199753662-668. 40. Clutton S: The importance of oxidative stress in apoptosis. Br Med Bull 1997;53:662–668.
41.
Halliwell BGutteridge JMCFree Radicals in Biology and Medicine4thClarendon PressOxford. 41. Halliwell B, and Gutteridge JMC: Free Radicals in Biology and Medicine, 4th ed. Clarendon Press, Oxford.
42.
Vaughan M. Oxidative modification of macromolecules, Minireviews SeriesJ Biol Chem199727218513. 42. Vaughan M: Oxidative modification of macromolecules, Minireviews Series. J Biol Chem 1997;272:18513.
43.
Sur JHDoster AROsorio FA. Apoptosis induced in vivo during acute infection by porcine reproductive and respiratory syndrome virusVet Pathol199835506-514. 43. Sur JH, Doster AR, and Osorio FA: Apoptosis induced in vivo during acute infection by porcine reproductive and respiratory syndrome virus. Vet Pathol 1998;35:506–514.
44.
Lin YWu D. All-trans retinoic acid regulates intracellular redox status in MARC-145 cells infected with porcine reproductive and respiratory syndrome virusTurk J Vet Anim Sci201034273-281. 44. Lin Y, and Wu D: All-trans retinoic acid regulates intracellular redox status in MARC-145 cells infected with porcine reproductive and respiratory syndrome virus. Turk J Vet Anim Sci 2010;34:273–281.

Information & Authors

Information

Published In

cover image Viral Immunology
Viral Immunology
Volume 24Issue Number 6December 2011
Pages: 475 - 482
PubMed: 22111597

History

Published online: 8 December 2011
Published in print: December 2011
Published ahead of print: 23 November 2011
Accepted: 23 July 2011
Received: 3 June 2011

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    Authors

    Affiliations

    Basavaraj Binjawadagi
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio.
    Varun Dwivedi
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio.
    Cordelia Manickam
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio.
    Jordi B. Torrelles
    Center for Microbial Interface Biology, Division of Infectious Diseases, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
    Gourapura J. Renukaradhya
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio.

    Notes

    Address correspondence to:Dr. Gourapura J. RenukaradhyaFood Animal Health Research ProgramOhio Agricultural Research and Development CenterThe Ohio State University1680 Madison AvenueWooster, OH 44691E-mail: [email protected]

    Author Disclosure Statement

    No competing financial interests exist.

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