Increased susceptibility of peripheral blood mononuclear cells to equine herpes virus type 1 infection upon mitogen stimulation: a role of the cell cycle and of cell-to-cell transmission of the virus.
Abstract: Equine herpesvirus-1 (EHV-1) is an important pathogen of horses, causing abortion and nervous system disorders, even in vaccinated animals. During the cell-associated viremia, EHV-1 is carried by peripheral blood mononuclear cells (PBMC), mainly lymphocytes. In vitro, monocytes are the most important fraction of PBMC in which EHV-1 replicates, however, mitogen stimulation prior to EHV-1 infection increases the percentage of infected lymphocytes. The role of the cell cycle in viral replication and the role of cluster formation in cell-to-cell transmission of the virus were examined in mitogen-stimulated PBMC. Involvement of the cell cycle was examined by stimulating PBMC with ionomycin/phorbol dibutyrate (IONO/PDB) during 0, 12, 24 and 36 h prior to inoculation. Cell cycle distribution at the moment of inoculation and the percentage of EHV-1 antigen-positive PBMC at 0, 12 and 24 hours post inoculation (hpi) were determined by flow cytometry and immunofluorescence microscopy, respectively. The role of clusters was examined by immunofluorescence staining within clusters of stimulated PBMC using antibodies against EHV-1. Significant correlations were found between the increase of cells in the S- or G2/M-phase after a certain time interval of prestimulation and the increase of EHV-1 antigen-positive cells. The percentage of clusters with adjacent infected cells significantly increased from 3.3% at 8 hpi to 23.7% at 24 hpi and the maximal number of adjacent infected cells increased from 2 to 7. Addition of anti-EHV-1 hyperimmune serum did not significantly alter these percentages. Mitogen stimulation favours EHV-1 infection in PBMC by: (i) initiating cell proliferation and (ii) inducing formation of clusters, thereby facilitating direct cell-associated transmission of virus.
Publication Date: 2002-03-13 PubMed ID: 11888698DOI: 10.1016/s0378-1135(01)00499-0Google Scholar: Lookup
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- Journal Article
Summary
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The abstract discusses a study that explores the heightened vulnerability of peripheral blood mononuclear cells (PBMC) to equine herpesvirus type 1 (EHV-1) infection, particularly following mitogen stimulation. It highlights how cell proliferation, cell cycling, and cell-to-cell transmission influence the infection spread of EHV-1.
Objectives of the Research
- The research aimed to understand the increased susceptibility of PBMC to EHV-1 following mitogen stimulation, a process artificially initiated for the study.
- The role of the cell cycle in EHV-1 replication and cell-to-cell transmission of the virus through cluster formation in stimulated PBMC was examined.
- The researchers studied the impact of stimulating PBMC with ionomycin/phorbol dibutyrate (IONO/PDB) on the cell cycle distribution and the percentage of EHV-1 antigen-positive PBMC.
Research Findings
- Cell cycle involvement was determined by observing changes in cell cycle distribution at the moment of inoculation and the percentage of EHV-1 antigen-positive PBMC at various time points post-inoculation.
- The study found significant correlations between an increase of cells in the S-phase or G2/M-phase following a set time of prestimulation, and the increase in EHV-1 antigen-positive cells.
- It was noted that the percentage of clusters with adjacent infected cells significantly increased over time, indicating the role of clustering in virus transmission.
- The research found that the addition of an anti-EHV-1 hyperimmune serum did not significantly alter these percentages, implying the limited efficacy of this serum in mitigating the effects of EHV-1 infection.
Conclusion
- The study concluded that mitogen stimulation increases the susceptibility of PBMC to EHV-1 infection by initiating cell proliferation and inducing the formation of clusters.
- This facilitates direct cell-to-cell transmission of the virus, thereby increasing the spread of the infection.
Cite This Article
APA
van der Meulen KM, Nauwynck HJ, Pensaert MB.
(2002).
Increased susceptibility of peripheral blood mononuclear cells to equine herpes virus type 1 infection upon mitogen stimulation: a role of the cell cycle and of cell-to-cell transmission of the virus.
Vet Microbiol, 86(1-2), 157-163.
https://doi.org/10.1016/s0378-1135(01)00499-0 Publication
Researcher Affiliations
- Faculty of Veterinary Medicine, Laboratory of Virology, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium.
MeSH Terms
- Animals
- Antigens, Viral / analysis
- Cell Aggregation / physiology
- Cell Cycle / physiology
- Flow Cytometry / veterinary
- Herpesviridae Infections / blood
- Herpesviridae Infections / pathology
- Herpesviridae Infections / veterinary
- Herpesviridae Infections / virology
- Herpesvirus 1, Equid / growth & development
- Horse Diseases / blood
- Horse Diseases / pathology
- Horse Diseases / virology
- Horses
- Ionomycin / pharmacology
- Ionophores / pharmacology
- Leukocytes, Mononuclear / cytology
- Leukocytes, Mononuclear / drug effects
- Leukocytes, Mononuclear / virology
- Lymphocyte Activation / drug effects
- Lymphocyte Activation / physiology
- Mitogens / pharmacology
- Phorbol 12,13-Dibutyrate / pharmacology
- Virus Replication / physiology
Citations
This article has been cited 3 times.- 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).
- Gönci B, Németh V, Balogh E, Szabó B, Dénes Á, Környei Z, Vicsek T. Viral epidemics in a cell culture: novel high resolution data and their interpretation by a percolation theory based model. PLoS One 2010 Dec 20;5(12):e15571.
- Dourmishev LA, Dourmishev AL, Palmeri D, Schwartz RA, Lukac DM. Molecular genetics of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) epidemiology and pathogenesis. Microbiol Mol Biol Rev 2003 Jun;67(2):175-212, table of contents.
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