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Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus

Published online by Cambridge University Press:  08 June 2015

Thomas R. Hansen ,
Natalia P. Smirnova ,
Brett T. Webb ,
Helle Bielefeldt-Ohmann ,
Randy E. Sacco  and
Hana Van Campen
Thomas R. Hansen*
Affiliation:
Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, CO 80523-1683, USA
Natalia P. Smirnova
Affiliation:
Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, CO 80523-1683, USA
Brett T. Webb
Affiliation:
Veterinary Diagnostic Laboratory, North Dakota State University, ND, 58108, USA
Helle Bielefeldt-Ohmann
Affiliation:
Australian Infectious Diseases Research Centre & School of Veterinary Science University of Queensland, Queensland, Australia
Randy E. Sacco
Affiliation:
Ruminant Diseases and Immunology Unit, National Animal Disease Center, USDA/ARS, IA 50010, USA
Hana Van Campen
Affiliation:
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, CO 80523-1683, USA
*
*Corresponding author. E-mail: thomas.hansen@colostate.edu
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Abstract

Infection of pregnant cows with noncytopathic (ncp) bovine viral diarrhea virus (BVDV) induces rapid innate and adaptive immune responses, resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent infection with ncpBVDV in the fetus has been attributed to the inability to mount an immune response before 90–150 days of gestational age. The result is ‘immune tolerance’, persistent viral replication and shedding of ncpBVDV. In contrast, we describe the chronic upregulation of fetal Type I interferon (IFN) pathway genes and the induction of IFN-γ pathways in fetuses of cows infected on day 75 of gestation. Persistently infected (PI) fetal IFN-γ concentrations also increased at day 97 at the peak of fetal viremia and IFN-γ mRNA was significantly elevated in fetal thymus, liver and spleen 14–22 days post maternal inoculation. PI fetuses respond to ncpBVDV infection through induction of Type I IFN and IFN-γ activated genes leading to a reduction in ncpBVDV titer. We hypothesize that fetal infection with BVDV persists because of impaired induction of IFN-γ in the face of activated Type I IFN responses. Clarification of the mechanisms involved in the IFN-associated pathways during BVDV fetal infection may lead to better detection methods, antiviral compounds and selection of genetically resistant breeding animals.

Keywords

innateadaptiveimmune responsebovine viral diarrhea viruspersistent infectioninterferonIFNfetus
Type
Review Article
Information
Animal Health Research Reviews , Volume 16 , Issue 1 , June 2015 , pp. 15 - 26
Copyright
Copyright © Cambridge University Press 2015 

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References

Alexopoulou, L, Holt, AC, Medzhitov, R and Flavell, RA (2001). Recognition of double-stranded RNA and activation of Nf-Kappab by toll-like receptor 3. Nature 413: 732–738.Google Scholar
Baigent, SJ, Zhang, G, Fray, MD, Flick-Smith, H, Goodbourn, S and McCauley, JW (2002). Inhibition of beta interferon transcription by noncytopathogenic bovine viral diarrhea virus is through an interferon regulatory factor 3-dependent mechanism. Journal of Virology 76: 8979–8988.CrossRefGoogle ScholarPubMed
Baigent, SJ, Goodbourn, S and McCauley, JW (2004). Differential activation of interferon regulatory factors-3 and -7 by non-cytopathogenic and cytopathogenic bovine viral diarrhoea virus. Veterinary Immunology and Immunopathology 100: 135–144.CrossRefGoogle ScholarPubMed
Bielefeldt Ohmann, H (1988a). BVD virus antigens in tissues of persistently viraemic, clinically normal cattle: implications for the pathogenesis of clinically fatal disease. Acta Veterinaria Scandinavica 29: 77–84.CrossRefGoogle ScholarPubMed
Bielefeldt Ohmann, H (1988b). In situ characterization of mononuclear leukocytes in skin and digestive tract of persistently bovine viral diarrhea virus-infected clinically healthy calves and calves with mucosal disease. Veterinary Pathology 25: 304–309.Google Scholar
Bielefeldt-Ohmann, H (1995). The pathologies of bovine viral diarrhea virus infection. A window on the pathogenesis. The Veterinary Clinics of North America 11: 447–476.Google ScholarPubMed
Bielefeldt-Ohmann, H, Tolnay, AE, Reisenhauer, CE, Hansen, TR, Smirnova, N and Van Campen, H (2008). Transplacental infection with non-cytopathic bovine viral diarrhoea virus Types 1b and 2: viral spread and molecular neuropathology. Journal of Comparative Pathology 138: 72–85.Google Scholar
Bielefeldt-Ohmann, H, Smirnova, NP, Tolnay, AE, Webb, BT, Antoniazzi, AQ, van Campen, H and Hansen, TR (2012). Neuro-invasion by a ‘trojan horse’ strategy and vasculopathy during intrauterine flavivirus infection. International Journal of Experimental Pathology 93: 24–33.CrossRefGoogle ScholarPubMed
Bilzer, M, Roggel, F and Gerbes, AL (2006). Role of Kupffer cells in host defense and liver disease. Liver International 26: 1175–1186.CrossRefGoogle ScholarPubMed
Brackenbury, LS, Carr, BV and Charleston, B (2003). Aspects of the innate and adaptive immune responses to acute infections with BVDV. Veterinary Microbiology 96: 337–344.CrossRefGoogle ScholarPubMed
Burciaga-Robles, LO, Step, DL, Krehbiel, CR, Holland, BP, Richards, CJ, Montelongo, MA, Confer, AW and Fulton, RW (2010). Effects of exposure to calves persistently infected with bovine viral diarrhea virus Type 1b and subsequent infection with Mannheimia haemolytica on clinical signs and immune variables: model for bovine respiratory disease via viral and bacterial interaction. Journal of Animal Science 88: 2166–2178.CrossRefGoogle ScholarPubMed
Chen, Z, Rijnbrand, R, Jangra, RK, Devaraj, SG, Qu, L, Ma, Y, Lemon, SM and Li, K (2007). Ubiquitination and proteasomal degradation of interferon regulatory factor-3 induced by Npro from a cytopathic bovine viral diarrhea virus. Virology 366: 277–292.CrossRefGoogle ScholarPubMed
Chucri, TM, Monteiro, JM, Lima, AR, Salvadori, ML, Kfoury, JR Jr and Miglino, MA (2010). A review of immune transfer by the placenta. Journal of Reproductive Immunology 87: 14–20.CrossRefGoogle ScholarPubMed
Collen, T, Douglas, AJ, Paton, DJ, Zhang, G and Morrison, WI (2000). Single amino acid differences are sufficient for CD4(+) T-cell recognition of a heterologous virus by cattle persistently infected with bovine viral diarrhea virus. Virology 276: 70–82.CrossRefGoogle ScholarPubMed
Dubovi, EJ (1994). Impact of bovine viral diarrhea virus on reproductive performance in cattle. The Veterinary Clinics of North America: Food Animal Practice 10: 503–514.Google Scholar
Fray, MD, Paton, DJ and Alenius, S (2000). The effects of bovine viral diarrhoea virus on cattle reproduction in relation to disease control. Animal Reproduction Science 60–61: 615–627.CrossRefGoogle ScholarPubMed
Fulton, RW, Briggs, RE, Ridpath, JF, Saliki, JT, Confer, AW, Payton, ME, Duff, GC, Step, DL and Walker, DA (2005). Transmission of bovine viral diarrhea virus 1b to susceptible and vaccinated calves by exposure to persistently infected calves. Canadian Journal of Veterinary Research Revue Canadienne de Recherche Veterinaire 69: 161–169.Google ScholarPubMed
Gil, LH, Ansari, IH, Vassilev, V, Liang, D, Lai, VC, Zhong, W, Hong, Z, Dubovi, EJ and Donis, RO (2006a). The amino-terminal domain of bovine viral diarrhea virus Npro protein is necessary for alpha/beta interferon antagonism. Journal of Virology 80: 900–911.Google Scholar
Gil, LH, van Olphen, AL, Mittal, SK and Donis, RO (2006b). Modulation of PKR activity in cells infected by bovine viral diarrhea virus. Virus Research 116: 69–77.CrossRefGoogle ScholarPubMed
Glickman, MH and Ciechanover, A (2002). The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiological Reviews 82: 373–428.CrossRefGoogle ScholarPubMed
Gunn, GJ, Stott, AW and Humphry, RW (2004). Modelling and costing BVD outbreaks in beef herds. Veterinary Journal 167: 143–149.CrossRefGoogle ScholarPubMed
Hansen, TR, Smirnova, NP, Van Campen, H, Shoemaker, ML, Ptitsyn, AA and Bielefeldt-Ohmann, H (2010). Maternal and fetal response to fetal persistent infection with bovine viral diarrhea virus. American Journal of Reproductive Immunology 64: 295–306.Google Scholar
Harding, MJ, Cao, X, Shams, H, Johnson, AF, Vassilev, VB, Gil, LH, Wheeler, DW, Haines, D, Sibert, GJ, Nelson, LD, Campos, M and Donis, RO (2002). Role of bovine viral diarrhea virus biotype in the establishment of fetal infections. American Journal of Veterinary Research 63: 1455–1463.CrossRefGoogle ScholarPubMed
Hay, WW Jr (1991). The placenta. Not just a conduit for maternal fuels. Diabetes 40 (Suppl 2): 44–50.CrossRefGoogle ScholarPubMed
Hessman, BE, Fulton, RW, Sjeklocha, DB, Murphy, TA, Ridpath, JF and Payton, ME (2009). Evaluation of economic effects and the health and performance of the general cattle population after exposure to cattle persistently infected with bovine viral diarrhea virus in a starter feedlot. American Journal of Veterinary Research 70: 73–85.CrossRefGoogle Scholar
Hilton, L, Moganeradj, K, Zhang, G, Chen, YH, Randall, RE, McCauley, JW and Goodbourn, S (2006). The Npro product of bovine viral diarrhea virus inhibits DNA binding by interferon regulatory factor 3 and targets it for proteasomal degradation. Journal of Virology 80: 11723–11732.CrossRefGoogle ScholarPubMed
Houe, H (1999). Epidemiological features and economical importance of Bovine Virus Diarrhoea Virus (BVDV) infections. Veterinary Microbiology 64: 89–107.CrossRefGoogle ScholarPubMed
Igwebuike, UM (2006). Trophoblast cells of ruminant placentas – a minireview. Animal Reproduction Science 93: 185–198.CrossRefGoogle ScholarPubMed
Iqbal, M, Poole, E, Goodbourn, S and McCauley, JW (2004). Role for bovine viral diarrhea virus Erns glycoprotein in the control of activation of beta interferon by double-stranded RNA. Journal of Virology 78: 136–145.CrossRefGoogle ScholarPubMed
Kitagawa, M, Suzuki, H, Adachi, Y, Nakamura, H, Yoshino, S and Sumida, T (2001). Interferon-gamma enhances interleukin 12 production in rheumatoid synovial cells via CD40–CD154 dependent and independent pathways. The Journal of Rheumatology 28: 1764–1771.Google ScholarPubMed
Knolle, P, Lohr, H, Treichel, U, Dienes, HP, Lohse, A, Schlaack, J and Gerken, G (1995). Parenchymal and nonparenchymal liver cells and their interaction in the local immune response. Zeitschrift fur Gastroenterologie 33: 613–620.Google Scholar
Kobayashi, KS and van den Elsen, PJ (2012). Nlrc5: a key regulator of MHC Class I-dependent immune responses. Nature Reviews Immunology 12: 813–820.CrossRefGoogle ScholarPubMed
Le Bon, A, Thompson, C, Kamphuis, E, Durand, V, Rossmann, C, Kalinke, U and Tough, DF (2006). Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by Type I IFN. Journal of Immunology 176: 2074–2078.Google Scholar
Leiser, R and Kaufmann, P (1994). Placental structure: in a comparative aspect. Experimental and Clinical Endocrinology 102: 122–134.CrossRefGoogle Scholar
Leiser, R, Krebs, C, Klisch, K, Ebert, B, Dantzer, V, Schuler, G and Hoffmann, B (1997). Fetal villosity and microvasculature of the bovine placentome in the second half of gestation. Journal of Anatomy 191 (Pt 4): 517–527.CrossRefGoogle ScholarPubMed
Loneragan, GH, Thomson, DU, Montgomery, DL, Mason, GL and Larson, RL (2005). Prevalence, outcome, and health consequences associated with persistent infection with bovine viral diarrhea virus in feedlot cattle. Journal of the American Veterinary Medical Association 226: 595–601.Google Scholar
Martin, SW and Bohac, JG (1986). The association between serological titers in infectious bovine rhinotracheitis virus, bovine virus diarrhea virus, parainfluenza-3 virus, respiratory syncytial virus and treatment for respiratory disease in Ontario feedlot calves. Canadian Journal of Veterinary Research = Revue Canadienne de Recherche Veterinaire 50: 351–358.Google ScholarPubMed
Meissner, TB, Li, A, Biswas, A, Lee, KH, Liu, YJ, Bayir, E, Iliopoulos, D, van den Elsen, PJ and Kobayashi, KS (2010). NLR family member NLRC5 is a transcriptional regulator of MHC Class I genes. Proceedings of the National Academy of Sciences of the United States of America 107: 13794–13799.CrossRefGoogle ScholarPubMed
Meissner, TB, Li, A and Kobayashi, KS (2012). Nlrc5: a newly discovered MHC Class I transactivator (Cita). Microbes and Infection/Institut Pasteur 14: 477–484.Google Scholar
Min, W, Pober, JS and Johnson, DR (1996). Kinetically coordinated induction of TAP1 and HLA Class I by IFN-gamma: the rapid induction of TAP1 by IFN-gamma is mediated by Stat1 alpha. Journal of Immunology 156: 3174–3183.CrossRefGoogle Scholar
Moerman, A, Straver, PJ, de Jong, MC, Quak, J, Baanvinger, T and van Oirschot, JT (1994). Clinical consequences of a bovine virus diarrhoea virus infection in a dairy herd: a longitudinal study. The Veterinary Quarterly 16: 115–119.CrossRefGoogle Scholar
Munoz-Zanzi, CA, Hietala, SK, Thurmond, MC and Johnson, WO (2003). Quantification, risk factors and health impact of natural congenital infection with bovine viral diarrhea virus in dairy calves. American Journal of Veterinary Research 64: 358–365.CrossRefGoogle ScholarPubMed
Neerincx, A, Castro, W, Guarda, G and Kufer, TA (2013). Nlrc5, at the heart of antigen presentation. Frontiers in Immunology 4: 397.CrossRefGoogle ScholarPubMed
Olafson, P, AD, M and FH, F (1946). An apparently new transmissible disease of cattle. Cornell Veterinarian 36: 205–213.Google Scholar
Oriss, TB, McCarthy, SA, Morel, BF, Campana, MA and Morel, PA (1997). Crossregulation between T helper cell (Th)1 and Th2: inhibition of Th2 proliferation by IFN-gamma involves interference with Il-1. Journal of Immunology 158: 3666–3672.CrossRefGoogle ScholarPubMed
Palomares, RA, Walz, HG and Brock, KV (2013). Expression of Type I interferon-induced antiviral state and pro-apoptosis markers during experimental infection with low or high virulence bovine viral diarrhea virus in beef calves. Virus Research 173: 260–269.CrossRefGoogle ScholarPubMed
Peterhans, E and Schweizer, M (2013). BVDV: a pestivirus inducing tolerance of the innate immune response. Biologicals: Journal of the International Association of Biological Standardization 41: 39–51.CrossRefGoogle ScholarPubMed
Peterhans, E, Jungi, TW and Schweizer, M (2003). BVDV and innate immunity. Biologicals 31: 107–112.CrossRefGoogle ScholarPubMed
Potgieter, LN (1995). Immunology of bovine viral diarrhea virus. The Veterinary Clinics of North America: Food Animal Practice 11: 501–520.Google ScholarPubMed
Ridpath, J (2010a). The contribution of infections with bovine viral diarrhea viruses to bovine respiratory disease. The Veterinary Clinics of North America: Food Animal Practice 26: 335–348.Google Scholar
Ridpath, JF (2010b). Bovine viral diarrhea virus: global status. The Veterinary Clinics of North America: Food Animal Practice 26: 105–121, table of contents.Google ScholarPubMed
Risalde, MA, Gomez-Villamandos, JC, Pedrera, M, Molina, V, Ceron, JJ, Martinez-Subiela, S and Sanchez-Cordon, PJ (2011). Hepatic immune response in calves during acute subclinical infection with bovine viral diarrhoea virus Type 1. Veterinary Journal 190: e110–e116.CrossRefGoogle ScholarPubMed
Saito, T and Gale, M Jr (2007). Principles of intracellular viral recognition. Current Opinion in Immunology 19: 17–23.CrossRefGoogle ScholarPubMed
Samuel, CE (2001). Antiviral actions of interferons. Clinical Microbiology Reviews 14: 778–809.CrossRefGoogle ScholarPubMed
Schoenborn, JR and Wilson, CB (2007). Regulation of interferon-gamma during innate and adaptive immune responses. Advances in Immunology 96: 41–101.CrossRefGoogle ScholarPubMed
Schweizer, M and Peterhans, E (2001). Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced apoptosis and interferon synthesis. Journal of Virology 75: 4692–4698.CrossRefGoogle ScholarPubMed
Schweizer, M, Matzener, P, Pfaffen, G, Stalder, H and Peterhans, E (2006). ‘Self’ and ‘Nonself’ Manipulation of interferon defense during persistent infection: bovine viral diarrhea virus resists alpha/beta interferon without blocking antiviral activity against unrelated viruses replicating in its host cells. Journal of Virology 80: 6926–6935.CrossRefGoogle ScholarPubMed
Shoemaker, ML, Smirnova, NP, Bielefeldt-Ohmann, H, Austin, KJ, van Olphen, A, Clapper, JA and Hansen, TR (2009). Differential expression of the Type I interferon pathway during persistent and transient bovine viral diarrhea virus infection. Journal of Interferon & Cytokine Research 29: 23–35.CrossRefGoogle ScholarPubMed
Smedsrod, B and Pertoft, H (1985). Preparation of pure hepatocytes and reticuloendothelial cells in high yield from a single rat liver by means of percoll centrifugation and selective adherence. Journal of Leukocyte Biology 38: 213–230.Google Scholar
Smirnova, NP, Bielefeldt-Ohmann, H, Van Campen, H, Austin, KJ, Han, H, Montgomery, DL, Shoemaker, ML, van Olphen, AL and Hansen, TR (2008). Acute non-cytopathic bovine viral diarrhea virus infection induces pronounced Type I interferon response in pregnant cows and fetuses. Virus Research 132: 49–58.CrossRefGoogle ScholarPubMed
Smirnova, NP, Ptitsyn, AA, Austin, KJ, Bielefeldt-Ohmann, H, Van Campen, H, Han, H, van Olphen, AL and Hansen, TR (2009). Persistent fetal infection with bovine viral diarrhea virus differentially affects maternal blood cell signal transduction pathways. Physiological Genomics 36: 129–139.CrossRefGoogle ScholarPubMed
Smirnova, NP, Webb, BT, Bielefeldt-Ohmann, H, Van Campen, H, Antoniazzi, AQ, Morarie, SE and Hansen, TR (2012). Development of fetal and placental innate immune responses during establishment of persistent infection with bovine viral diarrhea virus. Virus Research 167: 329–336.CrossRefGoogle ScholarPubMed
Smirnova, NP, Webb, BT, McGill, JL, Schaut, RG, Bielefeldt-Ohmann, H, Van Campen, H, Sacco, RE and Hansen, TR (2014). Induction of interferon-gamma and downstream pathways during establishment of fetal persistent infection with bovine viral diarrhea virus. Virus Research 183C: 95–106.Google Scholar
Smith, EJ, Marie, I, Prakash, A, Garcia-Sastre, A and Levy, DE (2001). IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or IκB kinase but is blocked by Vaccinia Virus E3l protein. Journal of Biological Chemistry 276: 8951–8957.CrossRefGoogle ScholarPubMed
Speer, CP (2003). Inflammation and Bronchopulmonary Dysplasia. Seminars in Neonatology 8: 29–38.Google Scholar
Stokstad, M and Loken, T (2002). Pestivirus in cattle: experimentally induced persistent infection in calves. Journal of Veterinary Medicine 49: 494–501.Google Scholar
Tamura, T, Yanai, H, Savitsky, D and Taniguchi, T (2008). The IRF family transcription factors in immunity and oncogenesis. Annual Review of Immunology 26: 535–584.CrossRefGoogle ScholarPubMed
Taniguchi, T, Ogasawara, K, Takaoka, A and Tanaka, N (2001). IRF family of transcription factors as regulators of host defense. Annual Review of Immunology 19: 623–655.CrossRefGoogle ScholarPubMed
Toder, V, Fein, A, Carp, H and Torchinsky, A (2003). TNF-alpha in pregnancy loss and embryo maldevelopment: a mediator of detrimental stimuli or a protector of the fetoplacental unit? Journal of Assisted Reproduction and Genetics 20: 73–81.CrossRefGoogle ScholarPubMed
Torres-Aguilar, H, Aguilar-Ruiz, SR, Gonzalez-Perez, G, Munguia, R, Bajana, S, Meraz-Rios, MA and Sanchez-Torres, C (2010). Tolerogenic dendritic cells generated with different immunosuppressive cytokines induce antigen-specific anergy and regulatory properties in memory CD4+ T cells. Journal of Immunology 184: 1765–1775.Google Scholar
Valle, PS, Skjerve, E, Martin, SW, Larssen, RB, Osteras, O and Nyberg, O (2005). Ten years of Bovine Virus Diarrhoea Virus (BVDV) control in Norway: a cost-benefit analysis. Preventive Veterinary Medicine 72: 189–207; discussion 215–189.CrossRefGoogle ScholarPubMed
Webb, BT, Norrdin, RW, Smirnova, NP, Van Campen, H, Weiner, CM, Antoniazzi, AQ, Bielefeldt-Ohmann, H and Hansen, TR (2012). Bovine viral diarrhea virus cyclically impairs long bone trabecular modeling in experimental persistently infected fetuses. Veterinary Pathology 49: 930–940.CrossRefGoogle ScholarPubMed
Yamane, D, Kato, K, Tohya, Y and Akashi, H (2008). The relationship between the viral RNA level and upregulation of innate immunity in spleen of cattle persistently infected with bovine viral diarrhea virus. Veterinary Microbiology 129: 69–79.CrossRefGoogle ScholarPubMed
Yeow, WS, Au, WC, Juang, YT, Fields, CD, Dent, CL, Gewert, DR and Pitha, PM (2000). Reconstitution of virus-mediated expression of interferon alpha genes in human fibroblast cells by ectopic interferon regulatory Factor-7. Journal of Biological Chemistry 275: 6313–6320.Google Scholar
Zhou, F (2009). Molecular mechanisms of IFN-gamma to up-regulate MHC Class I antigen processing and presentation. International Reviews of Immunology 28: 239–260.CrossRefGoogle ScholarPubMed