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Effect of Ligands to Toll-Like Receptors (TLR) 3, 7 and 9 on Mice Infected with Mouse Hepatitis Virus A59

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DOI: 10.4236/oji.2014.44015    2,703 Downloads   3,173 Views  

ABSTRACT

Mice infected with mouse hepatitis virus A59 (MHV-A59), an enveloped, positive-strand RNA Co-ronavirus, induce hepatitis, thymus involution, IgG2a-restricted hypergammaglobulinaemia, transaminase release and autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hy-drolase (FAH). Since Toll-like receptors (TLR) play a central role in innate immunity, we explored the effects of TLR3, 7 and 9 stimulation on MHV mouse infection. Thus, the animals were treated with Poly (I:C), Loxoribine and CpG, the respective TLR ligands. MHV-infected mice inoculated with Poly (I:C) had significant lower levels of plasma transaminases and Ig, anti-MHV Ab, and uric acid than MHV-infected animals, whereas autoAb to kidney tissue were observed. Loxoribine only produced a slight decrease of uric acid levels and serum Ig. CpG showed deleterious effects on MHV-infected mice, since survival of animals dramatically dropped to about 10%. AutoAb to murine tissues and uric acid release were not affected, whereas transaminases and anti-MHV Ab were slightly elevated. Besides, CpG administration produced a decrease of the high levels of serum Ig induced by the virus. Therefore, results indicated that TLR3 stimulation appeared to protect the animals against the viral infection, whereas CpG aggravated its signs. Loxoribine, the TLR7 ligand, did not show major effects.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Aparicio, J. , Vega, M. and Retegui, L. (2014) Effect of Ligands to Toll-Like Receptors (TLR) 3, 7 and 9 on Mice Infected with Mouse Hepatitis Virus A59. Open Journal of Immunology, 4, 129-138. doi: 10.4236/oji.2014.44015.

References

[1] Godfraind, C., Holmes, K.V. and Coutelier, J.-P. (1995) Thymus Involution Induced by Mouse Hepatitis Virus A59 in BALB/c Mice. Journal of Virology, 69, 6541-6547.
[2] Coutelier, J.-P., van der Logt, J.T., Heessen, F.W., Warnier, G. and Van Snick, J. (1987) IgG2a Restriction of Murine Antibodies Elicited by Viral Infections. Journal of Experimental Medicine, 165, 64-69.
http://dx.doi.org/10.1084/jem.165.1.64
[3] Lavi, E., Gilden, D.H., Wroblewska, Z., Rorke, L.B. and Weiss, S.R. (1984) Experimental Demyelination Produced by the A59 Strain of Mouse Hepatitis Virus. Neurology, 34, 597-603.
http://dx.doi.org/10.1212/WNL.34.5.597
[4] Mathieu, P.A., Gómez, K.A., Coutelier, J.-P. and Retegui, L.A. (2001) Identification of Two Liver Proteins Recognized by Autoantibodies Elicited in Mice Infected with Mouse Hepatitis Virus A59. European Journal of Immunology, 31, 1447-1455.
http://dx.doi.org/10.1002/1521-4141(200105)31:5<1447::AID-IMMU1447>3.0.CO;2-6
[5] Duhalde-Vega, M., Loureiro, M.E., Mathieu, P.A. and Retegui, L.A. (2006) The Peptide Specificities of the Autoantibodies Elicited by Mouse Hepatitis Virus A59. Journal of Autoimmunity, 27, 203-209.
http://dx.doi.org/10.1016/j.jaut.2006.09.003
[6] Duhalde-Vega, M., Aparicio, J.L. and Retegui, L.A. (2009) Fine Specificity of Autoantibodies Induced by Mouse Hepatitis Virus A59. Viral Immunology, 22, 287-294.
http://dx.doi.org/10.1089/vim.2009.0019
[7] Mathieu, P.A., Gómez, K.A., Coutelier, J.-P. and Retegui, L.A. (2004) Sequence Similarity and Structural Homologies Are Involved in the Autoimmune Response Elicited by Mouse Hepatitis Virus A59. Journal of Autoimmunity, 23, 117-126.
http://dx.doi.org/10.1016/j.jaut.2004.05.006
[8] Matzinger, P. (2002) The Danger Model: A Renewed Sense of Self. Science, 296, 301-305.
http://dx.doi.org/10.1126/science.1071059
[9] Duhalde-Vega, M. and Retegui, L.A. (2011) Uric Acid and HMGB1 Are Involved in the Induction of Autoantibodies Elicited in Mice Infected with Mouse Hepatitis Virus A59. Autoimmunity, 44, 631-640.
http://dx.doi.org/10.3109/08916934.2011.579927
[10] Aparicio, J.L., Duhalde-Vega, M., Loureiro, M.E. and Retegui, L.A. (2009) The Autoimmune Response Induced by Mouse Hepatitis Virus A59 Is Expanded by an Hepatotoxic Agent. International Immunopharmacology, 9, 627-631.
http://dx.doi.org/10.1016/j.intimp.2009.02.006
[11] Alexander, J., del Guercio, M.-F., Frame, B., Maewal, A., Sette, A., Nahm, M.H. and Newman, M.J. (2004) Development of Experimental Carbohydrate-Conjugate Vaccines Composed of Streptococcus pneumonia Capsular Polysaccharides and the Universal Helper T-Lymphocyte Epitope (PADRE). Vaccine, 22, 2362-2367.
http://dx.doi.org/10.1016/j.vaccine.2003.11.061
[12] Aparicio, J.L., Pena, C. and Retegui, L.A. (2011) Autoimmune Hepatitis-Like Disease in C57BL/6 Mice Infected with Mouse Hepatitis Virus A59. International Immunopharmacology, 11, 1591-1598.
http://dx.doi.org/10.1016/j.intimp.2011.05.020
[13] Carty, M. and Bowie, A.G. (2010) Recent Insights into the Role of Toll-Like Receptors in Viral Infection. Clinical and Experimental Immunology, 161, 397-406.
http://dx.doi.org/10.1111/j.1365-2249.2010.04196.x
[14] Connolly, D.J. and O’Neill, L.A.J. (2012) New Developments in Toll-Like Receptor Targeted Therapeutics. Current Opinion in Pharmacology, 12, 510-518.
http://dx.doi.org/10.1016/j.coph.2012.06.002
[15] Kawai, T. and Akira, S. (2010) The Role of Pattern-Recognition Receptors in Innate Immunity: Update on Toll-Like Receptors. Nature Immunology, 11, 373-384.
http://dx.doi.org/10.1038/ni.1863
[16] Kawai, T. and Akira, S. (2011) Toll-Like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immunity. Immunity, 34, 637-650.
http://dx.doi.org/10.1016/j.immuni.2011.05.006
[17] Coutelier, J.-P., Coulie, P.G., Wauters, P., Heremans, H. and van der Logt, J.T.M. (1990) In Vivo Polyclonal B-Lymphocyte Activation Elicited by Murine Viruses. Journal of Virology, 64, 5383-5388.
[18] Gustot, T., Lemmers, A., Moreno, C., Nagy, N., Quertinmont, E., Nicaise, C., Franchimont, D., Louis, H., Devière, J. and Le Moine, O. (2006) Differential Liver Sensitization to Toll-Like Receptor Pathways in Mice with Alcoholic Fatty Liver. Hepatology, 43, 989-1000.
http://dx.doi.org/10.1002/hep.21138
[19] Hayashia, T., Graya, C.S., Chana, M., Tawataoa, R.I., Ronacherb, L., McGargillc, M.A., Dattad, S.K., Carsona, D.A. and Corrb, M. (2009) Prevention of Autoimmune Disease by Induction of Tolerance to Toll-Like Receptor 7. Proceedings of the National Academy of Sciences of the United States of America, 24, 2764-2769.
http://dx.doi.org/10.1073/pnas.0813037106
[20] Bradford, M.M. (1976) A Rapid and Sensitive Method for the Quantification of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Analytical Biochemistry, 72, 248-254.
http://dx.doi.org/10.1016/0003-2697(76)90527-3
[21] Liu, G. and Zhao, Y. (2007) Toll-Like Receptors and Immune Regulation: Their Direct and Indirect Modulation on Regulatory CD4+ CD25+ T Cells. Immunology, 122, 149-156.
http://dx.doi.org/10.1111/j.1365-2567.2007.02651.x
[22] Mazaleuskaya, L., Veltrop, R., Ikpeze, N., Martin-Garcia, J. and Navas-Martin, S. (2012) Protective Role of Toll-Like Receptor 3-Induced Type I Interferon in Murine Coronavirus Infection of Macrophages. Viruses, 4, 901-923.
http://dx.doi.org/10.3390/v4050901
[23] He, J., Lang, G., Ding, S. and Li, L. (2013) Pathological Role of Interleukin-17 in Poly I:C-Induced Hepatitis. PLoS ONE, 8, e73909.
http://dx.doi.org/10.1371/journal.pone.0073909
[24] Walsh, K.B., Teijaro, J.R., Zuniga, E.I., Welch, M.J., Fremgen, D.M., Blackburn, S.D., von Tiehl, K.F., Wherry, E.J., Flavell, R.A. and Oldstone, M.B.A. (2012) Toll-Like Receptor 7 Is Required for Effective Adaptive Immune Responses that Prevent Persistent Virus Infection. Cell Host & Microbe, 11, 643-653.
http://dx.doi.org/10.1016/j.chom.2012.04.016
[25] Rajagopal, D., Paturel, C., Morel, Y., Uematsu, S., Akira, S. and Diebold, S.S. (2010) Plasmacytoid Dendritic Cell-Derived Type I Interferon Is Crucial for the Adjuvant Activity of Toll-Like Receptor 7 Agonists. Blood, 115, 1949- 1957.
http://dx.doi.org/10.1182/blood-2009-08-238543
[26] Jiang, W., Sun, R., Zhou, R., Wei, H. and Tian, Z. (2009) TLR-9 Activation Aggravates Concanavalin A-Induced Hepatitis via Promoting Accumulation and Activation of Liver CD4+ NKT Cells. Journal of Immunology, 182, 3768-3774.
http://dx.doi.org/10.4049/jimmunol.0800973
[27] Kaisho, T. (2012) Pathogen Sensors and Chemokine Receptors in Dendritic Cell Subsets. Vaccine, 30, 7652-7657.
http://dx.doi.org/10.1016/j.vaccine.2012.10.043
[28] Yang, H. and Tracey, K.J. (2010) Targeting HMGB1 in Inflammation. Biochimica et Biophysica Acta, 1799, 149-156.
http://dx.doi.org/10.1016/j.bbagrm.2009.11.019
[29] Holldack, J. (2014) Toll-Like Receptors as Therapeutic Targets for Cancer. Drug Discovery Today, 19, 379-382.
http://dx.doi.org/10.1016/j.drudis.2013.08.020

  
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