Mitogen stimulation favours replication of equine herpesvirus-1 in equine blood mononuclear cells by inducing cell proliferation and formation of close intercellular contacts
Abstract
In the present study, equine herpesvirus-1 (EHV-1)-infected cells were identified in ionomycin/phorbol dibutyrate (IONO/PDB)-stimulated peripheral blood mononuclear cells (PBMC) and the mechanism by which stimulation increases the percentage of infected cells was examined. In the population of viral antigen-positive PBMC, 38.4+/-4.5% were CD5(+) T-lymphocytes (18.1+/-3.2% CD4(+) 13.6+/-1.8% CD8(+)), 18.1+/-5.4% were B-lymphocytes, 8.5+/-3.9% were monocytes and 35% remained unidentified. The role of the cell cycle in the increased susceptibility to EHV-1 upon stimulation was examined by stimulating PBMC for 0, 12, 24 or 36 h prior to inoculation. A high correlation was found between the increase of cells in the S- (r=0.974) and G(2)/M-phase (r=0.927) at the moment of inoculation and the increase of infected cells at 12 h post-inoculation (p.i.). This suggests that a specific stage of the S-phase or S- and G(2)/M-phase facilitates virus replication. At 24 h p.i. lower correlations were found, suggesting that other effects are involved. From 12 h after addition of IONO/PDB, formation of clusters of PBMC became manifest. We examined whether close intercellular contacts in these clusters facilitated cell-to-cell transmission of EHV-1. Between 8 and 17 h p.i., the percentage of clusters containing adjacent infected cells increased from 1.6 to 13.4% and the maximal number of adjacent infected cells increased from two to four. Confocal microscopy visualized close intercellular contacts between adjacent infected cells. It can be concluded that mitogen stimulation favours EHV-1 infection of PBMC (i) by initiating specific cell cycle events and (ii) by inducing formation of clusters, thereby facilitating transmission of virus between cells.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CD172a+ monocytic cells are the principal carrier cell type for EHV-1 during primary infection.
“Monocytic cells (CD172a + ) have been shown to be the main carrier cell type of EHV-1 during primary infection (8, 9).”
From Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a <sup>+</sup> Monocytic Cells upon Adhesion to Endothelial Cells (2015) · cites this paper as [8]
The carbohydrate-rich ECM probably has a role in viral transfer between PBMC themselves.
“This carbohydrate-rich ECM not only has a role in virus transmission between PBMC and EC but also probably has a role in viral transfer between PBMC themselves as the PBMC tend to aggregate together in the infection than the non-infection state”
From Equid Herpesvirus-1 Exploits the Extracellular Matrix of Mononuclear Cells to Ensure Transport to Target Cells (2020) · cites this paper as van der Meulen et al., 2001
Cites
Schang, L. M., Phillips, J. J., & Schaffer, P. A. (1998) · Journal of Virology · doi:10.1128/jvi.72.7.5626-5637.1998 · Cited by 160 · see citing works
Buddaert, W., Reeth, K. V., & Pensaert, M. B. (1998) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-5331-1_59 · Cited by 159 · see citing works
Inhibition of Cellular Cdk2 Activity Blocks Human Cytomegalovirus Replication
Bresnahan, W. A., Boldogh, I. R., Chi, P., Thompson, E. A., & Albrecht, T. (1997) · Virology · doi:10.1006/viro.1997.8489 · Cited by 142 · see citing works
Adhesion molecules in cell interactions
Hogg, N., & Landis, R. C. (1993) · Current Opinion in Immunology · doi:10.1016/0952-7915(93)90057-y · Cited by 132 · see citing works
Schang, L. M., Rosenberg, A., & Schaffer, P. A. (2000) · Journal of Virology · doi:10.1128/jvi.74.5.2107-2120.2000 · Cited by 101 · see citing works
Fais, S., Capobianchi, M. R., Abbate, I., Castilletti, C., Gentile, M., Fei, P. C., Ameglio, F., & DIANZANI, F. (1995) · AIDS · doi:10.1097/00002030-199504000-00003 · Cited by 97 · see citing works
Schang, L. M., Rosenberg, A., & Schaffer, P. A. (1999) · Journal of Virology · doi:10.1128/jvi.73.3.2161-2172.1999 · Cited by 94 · see citing works
(1987) · PubMed · Cited by 82 · see citing works
Scott, J. C., Dutta, S. K., & Myrup, A. (1983) · American Journal of Veterinary Research · doi:10.2460/ajvr.1983.44.07.1344 · Cited by 71 · see citing works
Tsunetsugu‐Yokota, Y., Yasuda, S., Sugimoto, A. K., Yagi, T., Azuma, M., Yagita∥, H., Akagawa, K. S., & Takemori, T. (1997) · Virology · doi:10.1006/viro.1997.8895 · Cited by 67 · see citing works
Anderson, S. J., & Coleclough, C. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.10.5123 · Cited by 58 · see citing works
van der Meulen, K. M., Nauwynck, H. J., Buddaert, W., & Pensaert, M. B. (2000) · Microbiology · doi:10.1099/0022-1317-81-1-21 · Cited by 57 · see citing works
Self-citationSmith, D. J., Iqbal, J., Edington, N., Purewal, A., & Hamblin, A. S. (1998) · Journal of General Virology · doi:10.1099/0022-1317-79-12-2997 · Cited by 51 · see citing works
Duan, X., Nauwynck, H., Favoreel, H. W., & Pensaert, M. B. (1998) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-5331-1_11 · Cited by 51 · see citing works
Immunization of young horses against viral rhinopneumonitis.
DOLL, E. R., & Bryans, J. T. (1963) · PubMed · Cited by 35 · see citing works
Lawrence, W. C. (1971) · Journal of Virology · doi:10.1128/jvi.7.6.736-748.1971 · Cited by 30 · see citing works
The effect of EHV-1 infection upon circulating leucocyte populations in the natural equine host
McCulloch, J., Williamson, S. A., Powis, S. J., & Edington, N. (1993) · Veterinary Microbiology · doi:10.1016/0378-1135(93)90189-e · Cited by 29 · see citing works
Zhang, C. H., Grünig, G., Davis, W. C., & Antczak, D. F. (1994) · Veterinary Immunology and Immunopathology · doi:10.1016/0165-2427(94)90090-6 · Cited by 10 · see citing works
Flagged first, then by citations
1 of the 19 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Equine herpesvirus 1 and 4 infections: an update
van Maanen, C. (2002) · Veterinary Quarterly · doi:10.1080/01652176.2002.9695126 · Cited by 117 · see citing works
Equine Herpes Virus-1: Virus, Immunity and Vaccines
Paillot, R., Case, R., Ross, J., Newton, R., & Nugent, J. (2008) · The Open Veterinary Science Journal · doi:10.2174/1874318808002010068 · Cited by 78 · see citing works
Gryspeerdt, A. C., Vandekerckhove, A. P., Garré, B., Barbé, F., Van de Walle, G. R., & Nauwynck, H. J. (2010) · Veterinary Microbiology · doi:10.1016/j.vetmic.2009.10.015 · Cited by 69 · see citing works
Two-Dimensional Model for Liquid-Rocket Transverse Combustion Instability
Sirignano, W. A., & Popov, P. P. (2013) · AIAA Journal · doi:10.2514/1.j052512 · Cited by 52 · see citing works
van der Meulen, K. M., Nauwynck, H., & Pensaert, M. B. (2003) · Journal of General Virology · doi:10.1099/vir.0.18864-0 · Cited by 43 · see citing works
Dunowska, M. (2014) · New Zealand Veterinary Journal · doi:10.1080/00480169.2014.899946 · Cited by 40 · see citing works
Equine herpesvirus-1 infected peripheral blood mononuclear cell subpopulations during viremia
Wilsterman, S., Hussey, G. S., Lunn, D. P., Ashton, L. V., Callan, R. J., Hussey, S. B., Rao, S., & Goehring, L. S. (2010) · Veterinary Microbiology · doi:10.1016/j.vetmic.2010.10.004 · Cited by 39 · see citing works
Infection of central nervous system endothelial cells by cell-associated EHV-1
Goehring, L. S., Hussey, G. S., Ashton, L. V., Schenkel, A. R., & Lunn, D. P. (2011) · Veterinary Microbiology · doi:10.1016/j.vetmic.2010.08.030 · Cited by 34 · see citing works
New assays to measure equine influenza virus-specific Type 1 immunity in horses
Paillot, R., Kydd, J. H., MacRae, S., Minke, J. M. H. M., Hannant, D., & Daly, J. M. (2007) · Vaccine · doi:10.1016/j.vaccine.2007.08.033 · Cited by 29 · see citing works
Spiesschaert, B., Goldenbogen, B., Taferner, S., Schade, M., Mahmoud, M., Klipp, E., Osterrieder, N., & Azab, W. (2015) · Journal of Virology · doi:10.1128/jvi.01809-15 · Cited by 24 · see citing works
van der Meulen, K. M., Nauwynck, H., & Pensaert, M. B. (2002) · Veterinary Microbiology · doi:10.1016/s0378-1135(01)00499-0 · Cited by 11 · see citing works
Kamel, M., Pavulraj, S., Fauler, B., Mielke, T., & Azab, W. (2020) · iScience · doi:10.1016/j.isci.2020.101615 · Cited by 7 · see citing works
Wang, L. (2003) · Murdoch University Research Portal · Cited by 4 · see citing works
Kumar, M., Frid, O., Sol, A., Rouvinski, A., & Karniely, S. (2025) · Veterinary Research · doi:10.1186/s13567-025-01516-w · Cited by 3 · see citing works
Sáenz, J. R., Góez, Y., & Herrera, A. L. (2009) · Revista Colombiana de Ciencias Pecuarias · doi:10.17533/udea.rccp.324308 · Cited by 6 · see citing works
Interaction of equine herpesvirus 1 with equine peripheral blood mononuclear cells
van der Meulen, K. (2003) · Ghent University Academic Bibliography (Ghent University) · Cited by 1 · see citing works
- Authors
- van der Meulen, K. M., Nauwynck, H. J., & Pensaert, M. B.
- Affiliations
- Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium1
- Ghent University (BE)
- ORCID
- Nauwynck, Hans J.
- Venue
- Journal of General Virology
- Publisher
- Microbiology Society
- Published
- 2001-08-01
- Volume
- 82
- Issue
- 8
- Pages
- 1951-1957
- ISSN
- 0022-1317 (ISSN-L)
- 1465-2099
- OpenAlex
- W2138629532
- Cited by
- 16
- References
- 19
- Citations by year
- 2025: 1 · 2020: 1 · 2015: 1 · 2014: 1 · 2013: 1
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of General Virology (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Keywords
- equine herpesvirus 1, mitogen stimulation, peripheral blood mononuclear cells, cell cycle, S phase, G2/M phase, cell proliferation, cell-cell contact, cell-to-cell transmission, viral replication, B cells, monocytes
- MeSH terms
- Animals, B-Lymphocytes, Cell Aggregation, Cell Cycle, Herpesvirus 1, Equid, Herpesviridae Infections, Horses, Leukocytes, Mononuclear, Mitogens, Monocytes, Phorbol Esters, T-Lymphocytes, Virus Replication, CD4-Positive T-Lymphocytes, Ionomycin, CD8-Positive T-Lymphocytes, Lymphocyte Count, CD5 Antigens
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
