Analyze Diet
Immunology1997; 90(4); 586-591; doi: 10.1046/j.1365-2567.1997.00202.x

Transforming growth factor-beta induced by live or ultraviolet-inactivated equid herpes virus type-1 mediates immunosuppression in the horse.

Abstract: Up to 21 days after exposure to live or ultraviolet-inactivated equid herpesvirus type-1 (EHV-1) autologous serum from ponies caused an immunosuppressive effect if incorporated into T-cell proliferation assays to EHV-1. The suppressive factor in the sera of ponies also inhibited T-cell response to phytohaemagglutinin. Increased levels of circulating activated transforming growth factor-beta 1 (TGF-beta 1) were detected, and the suppressive activity of the serum could be reversed by antibody to TGF-beta 1. In a challenge experiment the ponies which exhibited circulating TGF-beta 1 activity succumbed to infection while the ones with similar magnitudes of T-cell responses, but no TGF-beta 1 activity, were protected. A definition of this immunosuppressive mechanism and its mode of induction must be central to the design of vaccines and to an understanding of the pathogenesis of EHV-1.
Publication Date: 1997-04-01 PubMed ID: 9176113PubMed Central: PMC1456683DOI: 10.1046/j.1365-2567.1997.00202.xGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses a study on the immunosuppressive effects of equid herpes virus type-1 (EHV-1) on horses, mediated by increased levels of the transforming growth factor-beta 1 (TGF-beta 1).

Research Context and Methodology

  • The study involves the equid herpes virus type-1 (EHV-1), a virus that can cause a variety of diseases in horses, including neurological disorders, respiratory diseases, and abortions.
  • The researchers exposed horses to live or ultraviolet-inactivated EHV-1 for up to 21 days. They then integrated the horses’ serum into T-cell proliferation assays to assess the effects on EHV-1.
  • The researchers also investigated the effect of the serum on T-cell response to phytohaemagglutinin, a substance known to stimulate T-cell proliferation.

Key Findings

  • The serum from the exposed horses caused suppression of the T-cell responses, hence an immunosuppressive effect. This was also evident in the response to phytohaemagglutinin, showing the general inhibitory impact on T-cell proliferation.
  • Increased levels of the transforming growth factor-beta 1 (TGF-beta 1) were observed upon exposure to the virus. TGF-beta 1 is a protein involved in cell differentiation and immune regulation, among other physiological processes.
  • This suppressive effect of the serum could be turned around by using an antibody to TGF-beta 1, indicating a significant role of TGF-beta 1 in mediating the immunosuppressive effects of EHV-1.
  • In a subsequent experiment, horses showing circulating TGF-beta 1 activity were found to succumb to infection, whereas those with similar magnitudes of T-cell responses but without TGF-beta 1 activity were protected against infection.

Conclusions and Implications

  • The research establishes the key role of TGF-beta 1 in mediating the immunosuppressive effects of the EHV-1 virus in horses. This discovery has significant implications for the understanding of EHV-1 pathogenesis.
  • Understanding this immunosuppressive mechanism could be central to designing vaccines against EHV-1. By targeting TGF-beta 1, it might be possible to reverse the inhibitory effects on T-cell proliferation and hence, enhance immune responses against the virus.

Cite This Article

APA
Charan S, Palmer K, Chester P, Mire-Sluis AR, Meager A, Edington N. (1997). Transforming growth factor-beta induced by live or ultraviolet-inactivated equid herpes virus type-1 mediates immunosuppression in the horse. Immunology, 90(4), 586-591. https://doi.org/10.1046/j.1365-2567.1997.00202.x

Publication

ISSN: 0019-2805
NlmUniqueID: 0374672
Country: England
Language: English
Volume: 90
Issue: 4
Pages: 586-591

Researcher Affiliations

Charan, S
  • Department of Pathology & Infectious Diseases, Royal Veterinary College, London, UK.
Palmer, K
    Chester, P
      Mire-Sluis, A R
        Meager, A
          Edington, N

            MeSH Terms

            • Animals
            • Herpesviridae Infections / immunology
            • Herpesviridae Infections / veterinary
            • Herpesvirus 1, Equid / immunology
            • Herpesvirus 1, Equid / radiation effects
            • Horse Diseases / immunology
            • Horses
            • Immune Tolerance
            • Lymphocyte Culture Test, Mixed
            • Polymerase Chain Reaction
            • Transforming Growth Factor beta / immunology
            • Ultraviolet Rays

            References

            This article includes 26 references
            1. Patel JR, Edington N, Mumford JA. Variation in cellular tropism between isolates of equine herpesvirus-1 in foals.. Arch Virol 1982;74(1):41-51.
              pubmed: 6297429doi: 10.1007/BF01320781google scholar: lookup
            2. Dutta SK, Myrup A, Bumgardner MK. Lymphocyte responses to virus and mitogen in ponies during experimental infection with equine herpesvirus 1.. Am J Vet Res 1980 Dec;41(12):2066-8.
              pubmed: 6259978
            3. Mumford JA, Bates J. Trials of an inactivated equid herpesvirus 1 vaccine: challenge with a subtype 2 virus.. Vet Rec 1984 Apr 14;114(15):375-81.
              pubmed: 6328729doi: 10.1136/vr.114.15.375google scholar: lookup
            4. Bridges CG, Edington N. Innate immunity during Equid herpesvirus 1 (EHV-1) infection.. Clin Exp Immunol 1986 Jul;65(1):172-81.
              pubmed: 2431815
            5. Mumford JA, Rossdale PD, Jessett DM, Gann SJ, Ousey J, Cook RF. Serological and virological investigations of an equid herpesvirus 1 (EHV-1) abortion storm on a stud farm in 1985.. J Reprod Fertil Suppl 1987;35:509-18.
              pubmed: 2824770
            6. Flanders KC, Roberts AB, Ling N, Fleurdelys BE, Sporn MB. Antibodies to peptide determinants in transforming growth factor beta and their applications.. Biochemistry 1988 Jan 26;27(2):739-46.
              pubmed: 2450577doi: 10.1021/bi00402a037google scholar: lookup
            7. Grotendorst GR, Smale G, Pencev D. Production of transforming growth factor beta by human peripheral blood monocytes and neutrophils.. J Cell Physiol 1989 Aug;140(2):396-402.
              pubmed: 2745570doi: 10.1002/jcp.1041400226google scholar: lookup
            8. Edington N, Bridges CG, Griffiths L. Equine interferons following exposure to equid herpesvirus-1 or -4.. J Interferon Res 1989 Aug;9(4):389-92.
              pubmed: 2474039doi: 10.1089/jir.1989.9.389google scholar: lookup
            9. Guo PX, Goebel S, Davis S, Perkus ME, Languet B, Desmettre P, Allen G, Paoletti E. Expression in recombinant vaccinia virus of the equine herpesvirus 1 gene encoding glycoprotein gp13 and protection of immunized animals.. J Virol 1989 Oct;63(10):4189-98.
            10. Fontana A, Frei K, Bodmer S, Hofer E, Schreier MH, Palladino MA Jr, Zinkernagel RM. Transforming growth factor-beta inhibits the generation of cytotoxic T cells in virus-infected mice.. J Immunol 1989 Nov 15;143(10):3230-4.
              pubmed: 2809199
            11. Allen GP, Bryans JT. Molecular epizootiology, pathogenesis, and prophylaxis of equine herpesvirus-1 infections.. Prog Vet Microbiol Immunol 1986;2:78-144.
              pubmed: 2856183
            12. Twardzik DR, Mikovits JA, Ranchalis JE, Purchio AF, Ellingsworth L, Ruscetti FW. Gamma-interferon-induced activation of latent transforming growth factor-beta by human monocytes.. Ann N Y Acad Sci 1990;593:276-84.
            13. Cook RF, O'Neill T, Strachan E, Sundquist B, Mumford JA. Protection against lethal equine herpes virus type 1 (subtype 1) infection in hamsters by immune stimulating complexes (ISCOMs) containing the major viral glycoproteins.. Vaccine 1990 Oct;8(5):491-6.
              pubmed: 2174599doi: 10.1016/0264-410x(90)90252-hgoogle scholar: lookup
            14. Bauer G, Götschl M, Höfler P. Tumor-promoting activity of Epstein-Barr-virus-inducing factor transforming growth factor type beta (EIF/TGF-beta) is due to the induction of irreversible transformation.. Int J Cancer 1991 Apr 1;47(6):881-8.
              pubmed: 1849123doi: 10.1002/ijc.2910470616google scholar: lookup
            15. Kuruvilla AP, Shah R, Hochwald GM, Liggitt HD, Palladino MA, Thorbecke GJ. Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice.. Proc Natl Acad Sci U S A 1991 Apr 1;88(7):2918-21.
              pubmed: 2011600doi: 10.1073/pnas.88.7.2918google scholar: lookup
            16. Stokes A, Corteyn AH, Pullen LA, Doel TR, Meredith DM, Killington RA, Halliburton IW, Whittaker GR, Wheldon LA, Nicolson L. Studies on glycoprotein 13 (gp13) of equid herpesvirus 1 using affinity-purified gp13, glycoprotein-specific monoclonal antibodies and synthetic peptides in a hamster model.. J Gen Virol 1991 Apr;72 ( Pt 4):923-31.
              pubmed: 1707948doi: 10.1099/0022-1317-72-4-923google scholar: lookup
            17. Meager A. Assays for transforming growth factor beta.. J Immunol Methods 1991 Jul 26;141(1):1-14.
              pubmed: 1865116doi: 10.1016/0022-1759(91)90204-sgoogle scholar: lookup
            18. O'Hagan DT, Jeffery H, Roberts MJ, McGee JP, Davis SS. Controlled release microparticles for vaccine development.. Vaccine 1991 Oct;9(10):768-71.
              pubmed: 1759495doi: 10.1016/0264-410x(91)90295-hgoogle scholar: lookup
            19. Woodroffe SB, Garnett HM, Danis VA. Interleukin-1 production and cell-activation response to cytomegalovirus infection of vascular endothelial cells.. Arch Virol 1993;133(3-4):295-308.
              pubmed: 8257291doi: 10.1007/BF01313770google scholar: lookup
            20. Rinaldo CR Jr, Torpey DJ 3rd. Cell-mediated immunity and immunosuppression in herpes simplex virus infection.. Immunodeficiency 1993;5(1):33-90.
              pubmed: 8167747
            21. Michelson S, Alcami J, Kim SJ, Danielpour D, Bachelerie F, Picard L, Bessia C, Paya C, Virelizier JL. Human cytomegalovirus infection induces transcription and secretion of transforming growth factor beta 1.. J Virol 1994 Sep;68(9):5730-7.
            22. Lowrance JH, O'Sullivan FX, Caver TE, Waegell W, Gresham HD. Spontaneous elaboration of transforming growth factor beta suppresses host defense against bacterial infection in autoimmune MRL/lpr mice.. J Exp Med 1994 Nov 1;180(5):1693-703.
              pubmed: 7964455doi: 10.1084/jem.180.5.1693google scholar: lookup
            23. Heise MT, Virgin HW 4th. The T-cell-independent role of gamma interferon and tumor necrosis factor alpha in macrophage activation during murine cytomegalovirus and herpes simplex virus infections.. J Virol 1995 Feb;69(2):904-9.
              pubmed: 7815559doi: 10.1128/JVI.69.2.904-909.1995google scholar: lookup
            24. Davignon JL, Castanié P, Yorke JA, Gautier N, Clément D, Davrinche C. Anti-human cytomegalovirus activity of cytokines produced by CD4+ T-cell clones specifically activated by IE1 peptides in vitro.. J Virol 1996 Apr;70(4):2162-9.
            25. Allison AC. Interactions of T-and B-lymphocytes and macrophages in recovery from virus infections.. Proc R Soc Med 1973 Dec;66(12):1151-4.
              pubmed: 4599617
            26. Burrows R, Goodridge D, Denyer MS. Trials of an inactivated equid herpesvirus 1 vaccine: challenge with a subtype 1 virus.. Vet Rec 1984 Apr 14;114(15):369-74.
              pubmed: 6328728doi: 10.1136/vr.114.15.369google scholar: lookup

            Citations

            This article has been cited 5 times.
            1. Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP. Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.. Vet Res 2011 Feb 7;42(1):23.
              doi: 10.1186/1297-9716-42-23pubmed: 21314906google scholar: lookup
            2. Allen CA, Payne SL, Harville M, Cohen N, Russell KE. Validation of quantitative polymerase chain reaction assays for measuring cytokine expression in equine macrophages.. J Immunol Methods 2007 Dec 1;328(1-2):59-69.
              doi: 10.1016/j.jim.2007.08.006pubmed: 17900609google scholar: lookup
            3. Smith D, Hamblin A, Edington N. Equid herpesvirus 1 infection of endothelial cells requires activation of putative adhesion molecules: an in vitro model.. Clin Exp Immunol 2002 Aug;129(2):281-7.
            4. Charleston B, Brackenbury LS, Carr BV, Fray MD, Hope JC, Howard CJ, Morrison WI. Alpha/beta and gamma interferons are induced by infection with noncytopathic bovine viral diarrhea virus in vivo.. J Virol 2002 Jan;76(2):923-7.
              doi: 10.1128/jvi.76.2.923-927.2002pubmed: 11752182google scholar: lookup
            5. Agarwal R, Elbishbishi EA, Chaturvedi UC, Nagar R, Mustafa AS. Profile of transforming growth factor-beta 1 in patients with dengue haemorrhagic fever.. Int J Exp Pathol 1999 Jun;80(3):143-9.