MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENES
Abstract. Cytomegalovirus (CMV) infection in diploid human fibroblasts (HF) and levels of cell resistance to this virus were shown to be in direct correlation with high α-interferon (IFNα) gene activity and induction of IFNγ gene transcription. Regulation of IFNα mRNA transcription was revealed to b...
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Format: | Article |
Language: | Russian |
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St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists
2014-07-01
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Series: | Медицинская иммунология |
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Online Access: | https://www.mimmun.ru/mimmun/article/view/206 |
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author | T. M. Sokolova N. E. Fedorova M. G. Medjidova S. M. Terekhov L. V. Uryvaev A. A. Kushch |
author_facet | T. M. Sokolova N. E. Fedorova M. G. Medjidova S. M. Terekhov L. V. Uryvaev A. A. Kushch |
author_sort | T. M. Sokolova |
collection | DOAJ |
description | Abstract. Cytomegalovirus (CMV) infection in diploid human fibroblasts (HF) and levels of cell resistance to this virus were shown to be in direct correlation with high α-interferon (IFNα) gene activity and induction of IFNγ gene transcription. Regulation of IFNα mRNA transcription was revealed to be positively associated with cellular DNA synthesis. At the same time, activities of IFNβ and IFNγ genes were at the constantly low level and were not induced in DNA-synthetic phase (S-phase) of the cells. Levels of IFNα mRNA synthesis are quite different for G0- vs S-phase-synchronized HF110044 cell cultures: appropriate values for dividing cells (S-phase) proved to be 100-fold higher than in resting state (G0). The mode of CMV infection in resting HF-cell could be considered either as acute, or a productive one. On the contrary, proliferating cells exhibited lagging viral syntheses and delayed cell death. Arrest of CMV replication may be, to some extent, comparable with latent infectious state, being associated with high production of IFNα. Both basal and induced levels of IFNα mRNA in CMV-resistant adult human skin fibroblast cells (HSF-1608) were 10-fold higher than in human embryo lung cell line (HELF-977), which is highly sensitive to CMV. Moreover, a short-time induction of IFNγ genes was observed in resistant cells, whereas no such effect was noticed in highly sensitive cells. CMV reproduction in sensitive cell lines (HELF-977 and HELF-110044) partially inhibits IFNα mRNA transcription at the later stages of infection (24 to 48 hours). Thus, cellular resistance and control of CMV infection in diploid fibroblasts are associated predominantly with high transcription of IFNα gene, and with temporal induction of IFNγ gene. We did not reveal any participation of IFNβ genes in protection of human diploid fibroblasts from CMV. |
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language | Russian |
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publishDate | 2014-07-01 |
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spelling | doaj.art-0020f1c6cb6c4ec3a7c1421d867175e02024-04-22T13:07:34ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2014-07-0194-545746610.15789/1563-0625-2007-4-5-457-466203MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENEST. M. Sokolova0N. E. Fedorova1M. G. Medjidova2S. M. Terekhov3L. V. Uryvaev4A. A. Kushch5ГУ НИИ вирусологии им. Д.И. Ивановского РАМН, МоскваГУ НИИ вирусологии им. Д.И. Ивановского РАМН, МоскваГУ НИИ вирусологии им. Д.И. Ивановского РАМН, МоскваМедико-генетический центр РАМН, МоскваГУ НИИ вирусологии им. Д.И. Ивановского РАМН, МоскваГУ НИИ вирусологии им. Д.И. Ивановского РАМН, МоскваAbstract. Cytomegalovirus (CMV) infection in diploid human fibroblasts (HF) and levels of cell resistance to this virus were shown to be in direct correlation with high α-interferon (IFNα) gene activity and induction of IFNγ gene transcription. Regulation of IFNα mRNA transcription was revealed to be positively associated with cellular DNA synthesis. At the same time, activities of IFNβ and IFNγ genes were at the constantly low level and were not induced in DNA-synthetic phase (S-phase) of the cells. Levels of IFNα mRNA synthesis are quite different for G0- vs S-phase-synchronized HF110044 cell cultures: appropriate values for dividing cells (S-phase) proved to be 100-fold higher than in resting state (G0). The mode of CMV infection in resting HF-cell could be considered either as acute, or a productive one. On the contrary, proliferating cells exhibited lagging viral syntheses and delayed cell death. Arrest of CMV replication may be, to some extent, comparable with latent infectious state, being associated with high production of IFNα. Both basal and induced levels of IFNα mRNA in CMV-resistant adult human skin fibroblast cells (HSF-1608) were 10-fold higher than in human embryo lung cell line (HELF-977), which is highly sensitive to CMV. Moreover, a short-time induction of IFNγ genes was observed in resistant cells, whereas no such effect was noticed in highly sensitive cells. CMV reproduction in sensitive cell lines (HELF-977 and HELF-110044) partially inhibits IFNα mRNA transcription at the later stages of infection (24 to 48 hours). Thus, cellular resistance and control of CMV infection in diploid fibroblasts are associated predominantly with high transcription of IFNα gene, and with temporal induction of IFNγ gene. We did not reveal any participation of IFNβ genes in protection of human diploid fibroblasts from CMV.https://www.mimmun.ru/mimmun/article/view/206human fibroblastsinterferonmrna transcriptioncytomegalovirus infection |
spellingShingle | T. M. Sokolova N. E. Fedorova M. G. Medjidova S. M. Terekhov L. V. Uryvaev A. A. Kushch MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENES Медицинская иммунология human fibroblasts interferon mrna transcription cytomegalovirus infection |
title | MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENES |
title_full | MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENES |
title_fullStr | MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENES |
title_full_unstemmed | MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENES |
title_short | MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENES |
title_sort | mechanisms of cell resistance to cytomegalovirus are connected with cell proliferation state and transcription activity of leukocyte and immune interferon genes |
topic | human fibroblasts interferon mrna transcription cytomegalovirus infection |
url | https://www.mimmun.ru/mimmun/article/view/206 |
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