Equid herpesvirus 1 infection of endothelial cells requires activation of putative adhesion molecules: an in vitro model.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research study investigates the role of endothelial adhesion molecules in equine herpesvirus 1 infection and demonstrates that these molecules play a key part in the transmission of the virus to endothelial cells in horses.
Objective
The main objective of this research was to understand the role of endothelial adhesion molecules in the infection process of equine herpesvirus 1. These molecules – of size 116 kD, 97 kD, 42 kD, and 38 kD – represented on the surface of activated equine endothelial cells, were induced and their interaction with the virus was studied in an in vitro flow system based on equine veins or arteries.
- The exact mechanism of equine herpesvirus 1 transmission to endothelial cells was a focal point of inquiry.
- These endothelial adhesion molecules were stimulated using 17-beta oestradiol, chorionic gonadotrophin, or IL-2, along with lipopolysaccharides (LPS) and pokeweed mitogen (PWM).
Methodology & Findings
Experiments revealed that the equine herpesvirus 1 could only infect endothelial cells when both leucocytes (white blood cells) and the endothelial cells displayed these surface molecules. Should these conditions be met, the virus housed in leucocytes gets transferred to the endothelial cells.
- Polyclonal antibodies were then used to block these membrane molecules to study the effect on the virus transfer.
- The research found that the blocking of these molecules halted the transfer of virus to endothelial cells.
- Therefore, it was concluded that the presence of these adhesion molecules is crucial for transferring the herpesvirus 1 from leucocytes to endothelial cells.
Conclusion
This study shed light on the reasons why in real-world instances, the herpesvirus 1 infects endothelial cells in specific tissues. The paper’s findings also pointed towards a much greater complexity in the series of factors that influence tissue tropism, which is the phenomenon of viruses infecting specific types of cells or tissue.
Additionally, the outcomes of this research provide potential avenues for further investigation on equine herpesvirus 1 infection and may contribute to the development of treatment strategies targeting these adhesion molecules.
Cite This Article
Publication
Researcher Affiliations
- Department of Pathology & Infectious Diseases, Royal Veterinary College, London, UK.
MeSH Terms
- Animals
- Antibodies
- Cell Adhesion
- Cell Adhesion Molecules / immunology
- Endothelium, Vascular / immunology
- Endothelium, Vascular / pathology
- Endothelium, Vascular / virology
- Female
- Herpesviridae Infections / etiology
- Herpesviridae Infections / immunology
- Herpesviridae Infections / pathology
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid
- Horse Diseases / etiology
- Horse Diseases / immunology
- Horse Diseases / pathology
- Horse Diseases / virology
- Horses
- In Vitro Techniques
- Leukocytes / immunology
- Leukocytes / pathology
- Leukocytes / virology
References
- Allen GP, Bryans JT. Molecular epizootiology, pathogenesis, and prophylaxis of equine herpesvirus-1 infections.. Prog Vet Microbiol Immunol 1986;2:78-144.
- Bumgardner MK, Dutta SK, Campbell DL, Myrup AC. Lymphocytes from ponies experimentally infected with equine herpesvirus 1: subpopulation dynamics and their response to mitogens.. Am J Vet Res 1982 Jul;43(7):1308-10.
- Scott JC, Dutta SK, Myrup AC. In vivo harboring of equine herpesvirus-1 in leukocyte populations and subpopulations and their quantitation from experimentally infected ponies.. Am J Vet Res 1983 Jul;44(7):1344-8.
- Jackson TA, Osburn BI, Cordy DR, Kendrick JW. Equine herpesvirus 1 infection of horses: studies on the experimentally induced neurologic disease.. Am J Vet Res 1977 Jun;38(6):709-19.
- 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.
- Edington N, Bridges CG, Patel JR. Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: equine stroke.. Arch Virol 1986;90(1-2):111-24.
- Edington N, Smyth B, Griffiths L. The role of endothelial cell infection in the endometrium, placenta and foetus of equid herpesvirus 1 (EHV-1) abortions.. J Comp Pathol 1991 May;104(4):379-87.
- Whitwell KE, Blunden AS. Pathological findings in horses dying during an outbreak of the paralytic form of Equid herpesvirus type 1 (EHV-1) infection.. Equine Vet J 1992 Jan;24(1):13-9.
- Smith KC, Whitwell KE, Binns MM, Dolby CA, Hannant D, Mumford JA. Abortion of virologically negative foetuses following experimental challenge of pregnant pony mares with equid herpesvirus 1.. Equine Vet J 1992 Jul;24(4):256-9.
- Phinney PR, Fligiel S, Bryson YJ, Porter DD. Necrotizing vasculitis in a case of disseminated neonatal herpes simplex infection.. Arch Pathol Lab Med 1982 Feb;106(2):64-7.
- Carmichael LE, Squire RA, Krook L. Clinical and pathologic features of a fatal viral disease of newborn pups.. Am J Vet Res 1965 Jul;26(113):803-14.
- Hashimoto A, Hirai K, Okada K, Fujimoto Y. Pathology of the placenta and newborn pups with suspected intrauterine infection of canine herpesvirus.. Am J Vet Res 1979 Sep;40(9):1236-40.
- Edington N, Plowright W, Watt RG. Generalized porcine cytomegalic inclusion disease: distribution of cytomegalic cells and virus.. J Comp Pathol 1976 Apr;86(2):191-202.
- Hanshaw JB. Congenital cytomegalovirus infection: a fifteen year perspective.. J Infect Dis 1971 May;123(5):555-61.
- Preece PM, Blount JM, Glover J, Fletcher GM, Peckham CS, Griffiths PD. The consequences of primary cytomegalovirus infection in pregnancy.. Arch Dis Child 1983 Dec;58(12):970-5.
- Pober JS, Bevilacqua MP, Mendrick DL, Lapierre LA, Fiers W, Gimbrone MA Jr. Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells.. J Immunol 1986 Mar 1;136(5):1680-7.
- Smith DJ, Iqbal J, Purewal A, Hamblin AS, Edington N. In vitro reactivation of latent equid herpesvirus-1 from CD5+/CD8+ leukocytes indirectly by IL-2 or chorionic gonadotrophin.. J Gen Virol 1998 Dec;79 ( Pt 12):2997-3004.
- Bridges CG, Edington N. Genetic restriction of cytolysis during equid herpesvirus 1 subtype 2 infection.. Clin Exp Immunol 1987 Nov;70(2):276-82.
- 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.
- Charan S, Palmer K, Chester P, Mire-Sluis AR, Meager A, Edington N. Transforming growth factor-beta induced by live or ultraviolet-inactivated equid herpes virus type-1 mediates immunosuppression in the horse.. Immunology 1997 Apr;90(4):586-91.
- Simmons DL, Needham L. Cloning cell surface molecules using monoclonal antibodies. In: Gordon JL, editor. Vascular Endothelium: Interactions with Circulating Cells. Amsterdam: Elsevier; 1991. p. 163.
- Craigen JL, Grundy JE. Cytomegalovirus induced up-regulation of LFA-3 (CD58) and ICAM-1 (CD54) is a direct viral effect that is not prevented by ganciclovir or foscarnet treatment.. Transplantation 1996 Oct 27;62(8):1102-8.
- Brankin B, Hart MN, Cosby SL, Fabry Z, Allen IV. Adhesion molecule expression and lymphocyte adhesion to cerebral endothelium: effects of measles virus and herpes simplex 1 virus.. J Neuroimmunol 1995 Jan;56(1):1-8.
- Soilu-Hänninen M, Röyttä M, Salmi AA, Salonen R. Semliki Forest virus infection leads to increased expression of adhesion molecules on splenic T-cells and on brain vascular endothelium.. J Neurovirol 1997 Oct;3(5):350-60.
- Shen J, T-To SS, Schrieber L, King NJ. Early E-selectin, VCAM-1, ICAM-1, and late major histocompatibility complex antigen induction on human endothelial cells by flavivirus and comodulation of adhesion molecule expression by immune cytokines.. J Virol 1997 Dec;71(12):9323-32.
- Ohrui T, Yamaya M, Sekizawa K, Terajima M, Yamada N, Suzuki T, Okinaga S, Hoshi H, Suzuki H, Sasaki H. [Rhinovirus infection and expression of adhesion molecules in human tracheal epithelium].. Nihon Kyobu Shikkan Gakkai Zasshi 1996 Dec;34 Suppl:121-5.
- Li E, Stupack D, Klemke R, Cheresh DA, Nemerow GR. Adenovirus endocytosis via alpha(v) integrins requires phosphoinositide-3-OH kinase.. J Virol 1998 Mar;72(3):2055-61.
- Smith D. The interactions of Equid herpes virus-1 infected leucocytes with equine endothelial cells. PhD Thesis.
- Lyall F, Greer IA, Boswell F, Young A, Macara LM, Jeffers MD. Expression of cell adhesion molecules in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth retardation.. Placenta 1995 Oct;16(7):579-87.
- Pober JS, Lapierre LA, Stolpen AH, Brock TA, Springer TA, Fiers W, Bevilacqua MP, Mendrick DL, Gimbrone MA Jr. Activation of cultured human endothelial cells by recombinant lymphotoxin: comparison with tumor necrosis factor and interleukin 1 species.. J Immunol 1987 May 15;138(10):3319-24.
Citations
This article has been cited 8 times.- Laval K, Poelaert KCK, Van Cleemput J, Zhao J, Vandekerckhove AP, Gryspeerdt AC, Garré B, van der Meulen K, Baghi HB, Dubale HN, Zarak I, Van Crombrugge E, Nauwynck HJ. The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1. Front Microbiol 2021;12:662686.
- Pavulraj S, Kamel M, Stephanowitz H, Liu F, Plendl J, Osterrieder N, Azab W. Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs. Viruses 2020 Sep 8;12(9).
- Kamel M, Pavulraj S, Osterrieder K, Azab W. EHV-1 Pathogenesis: Current in vitro Models and Future Perspectives. Front Vet Sci 2019;6:251.
- Van Cleemput J, Poelaert KCK, Laval K, Maes R, Hussey GS, Van den Broeck W, Nauwynck HJ. Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions. Sci Rep 2017 Nov 30;7(1):16656.
- Spiesschaert B, Goldenbogen B, Taferner S, Schade M, Mahmoud M, Klipp E, Osterrieder N, Azab W. Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: a Dynamic In Vitro Model. J Virol 2015 Dec;89(23):11899-908.
- Yeo WM, Osterrieder N, Stokol T. Equine herpesvirus type 1 infection induces procoagulant activity in equine monocytes. Vet Res 2013 Mar 11;44(1):16.
- Cooper CJ, Arroyo LG, Hammermueller JD, Botts MM, Pearl DL, Wootton SK, Lillie BN. Molecular prevalence of equine alphaherpesvirus-1 shedding in healthy broodmares in Ontario. Can J Vet Res 2026 Jan;90(1):16-24.
- Lessiak U, Melchert M, Walter I, Kummer S, Nell B, Tschulenk W, Pratscher B. Isolation-protocol, characterization, and in-vitro performance of equine umbilical vein endothelial cells. Front Vet Sci 2024;11:1421946.