In vitro reactivation of latent equid herpesvirus-1 from CD5+/CD8+ leukocytes indirectly by IL-2 or chorionic gonadotrophin.
Abstract: IL-2 and equine chorionic gonadotrophin (eCG) initiated reactivation of equid herpesvirus-1 (EHV-1) from venous lymphocytes at a frequency of 1/10(-5). Indirect immunofluorescence showed that > 80% of virus-positive leukocytes were CD5+/CD8+ with the remaining 20% being CD5+/CD8-/CD4-. Cocultivation demonstrated that the reactivated virus was infectious. In addition, virus was reactivated in vitro from leukocytes of > 70% of horses by the mitogens phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). Transfer of supernatants showed that IL-2 and eCG acted indirectly by causing the release of other mediators from adherent cells; these mediators then reactivated EHV-1 from T cells. Blocking experiments with anti-IL-2 showed that PWM and PHA acted via IL-2 but that eCG did not. This is the first clear definition of the lymphoid cells that harbour latent EHV-1 in vivo and correlates with current RT-PCR and in situ hybridization of latency-associated transcripts in lymphocytes. This method of reactivation in vitro can be used to detect horses carrying latent EHV-1 in vivo and also has the potential to dissect the sequence of events involved in reactivation in vitro.
Publication Date: 1999-01-08 PubMed ID: 9880014DOI: 10.1099/0022-1317-79-12-2997Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates how the Interleukin-2 (IL-2) and equine chorionic gonadotrophin (eCG) can reactivate the equid herpesvirus-1 (EHV-1) in CD5+/CD8+ leukocytes from horses. Reactivation in this case implies a stimulation of the virus from its dormant state. This research offers insights into the cells that serve as hosts for EHV-1 in horses, and could offer new methods to detect and study the virus.
Study Background and Methodology
- The researchers examined how two substances, Interleukin-2 (IL-2) and equine chorionic gonadotrophin (eCG), could stimulate the reactivation of equid herpesvirus-1 (EHV-1).
- This reactivation was tested from venous lymphocytes at a frequency of 1/10(-5).
- The reactivation process was analyzed using indirect immunofluorescence, a technique used to visualize the distribution of proteins in cells.
Major Findings
- They found that more than 80% of virus-positive leukocytes were CD5+/CD8+ with the remaining 20% being CD5+/CD8-/CD4-.
- The reactivated virus was infectious when co-cultivated, confirming the successful reactivation process.
- Additionally, it was discovered that the virus can be reactivated in vitro from leukocytes of more than 70% of horses by the mitogens phytohaemagglutinin (PHA) and pokeweed mitogen (PWM).
A Closer Look at Reactivation Process
- The information suggests that IL-2 and eCG worked indirectly, inciting the release of other mediators from adherent cells. These mediators then reactivated EHV-1 from T cells.
- Further experiments blocking IL-2 demonstrate how PWM and PHA stimulate the virus via IL-2, but eCG does not follow this mechanism.
- This research gives the first clear define of the lymphoid cells that host latent EHV-1 in horses. The results coordinate with current RT-PCR and in situ hybridization of latency-associated transcripts in lymphocytes.
Implications and Future Directions
- The method of reactivation in vitro established in this research can be used to detect horses carrying latent EHV-1, providing a new diagnostic tool.
- Moreover, it also offers potential for further exploration of the sequence of events involved in the reactivation process in vitro, providing an experimental platform for potential future interventions and treatments.
Cite This Article
APA
Smith DJ, Iqbal J, Purewal A, Hamblin AS, Edington N.
(1999).
In vitro reactivation of latent equid herpesvirus-1 from CD5+/CD8+ leukocytes indirectly by IL-2 or chorionic gonadotrophin.
J Gen Virol, 79 ( Pt 12), 2997-3004.
https://doi.org/10.1099/0022-1317-79-12-2997 Publication
Researcher Affiliations
- Department of Pathology and Infectious Diseases, Royal Veterinary College, London, UK.
MeSH Terms
- Animals
- CD5 Antigens
- CD8-Positive T-Lymphocytes / virology
- Cells, Cultured
- Chorionic Gonadotropin / metabolism
- Chorionic Gonadotropin / pharmacology
- Herpesvirus 1, Equid / growth & development
- Herpesvirus 1, Equid / physiology
- Horses
- Humans
- Interleukin-2 / metabolism
- Interleukin-2 / pharmacology
- Polymerase Chain Reaction
- Rabbits
- Virus Activation
- Virus Latency
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.
- Giessler KS, Samoilowa S, Soboll Hussey G, Kiupel M, Matiasek K, Sledge DG, Liesche F, Schlegel J, Fux R, Goehring LS. Viral Load and Cell Tropism During Early Latent Equid Herpesvirus 1 Infection Differ Over Time in Lymphoid and Neural Tissue Samples From Experimentally Infected Horses.. Front Vet Sci 2020;7:621.
- Oladunni FS, Horohov DW, Chambers TM. EHV-1: A Constant Threat to the Horse Industry.. Front Microbiol 2019;10:2668.
- Stokol T, Serpa PBS, Brooks MB, Divers T, Ness S. Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation.. Front Vet Sci 2018;5:106.
- Tallmadge RL, Žygelytė E, Van de Walle GR, Kristie TM, Felippe MJB. Effect of a Histone Demethylase Inhibitor on Equine Herpesvirus-1 Activity In Vitro.. Front Vet Sci 2018;5:34.
- Abdelgawad A, Damiani A, Ho SY, Strauss G, Szentiks CA, East ML, Osterrieder N, Greenwood AD. Zebra Alphaherpesviruses (EHV-1 and EHV-9): Genetic Diversity, Latency and Co-Infections.. Viruses 2016 Sep 20;8(9).
- 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.
- 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.
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