期刊
FRONTIERS IN MICROBIOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2021.784070
关键词
Dengue virus replication; megakaryopoiesis; reactive oxygen species; flavivirus
类别
资金
- University Grants Commission
- Department of Biotechnology, Govt of India [BT/PR22985/MED/29/1168/2016]
- Science and Engineering Research Board, Department of Science and Technology, Govt. of India [EMR/2016/005796]
In this study, it was found that Dengue virus can infect human megakaryocytes and suppress platelet biogenesis. Differentiating megakaryocyte cells were shown to support higher viral replication, while the virus did not increase its entry into the cells. Dengue replication inhibited the accumulation of intracellular reactive oxygen species (ROS) by enhancing the activity of the transcription factor NFE2L2. Interestingly, modulation of NFE2L2 activity had opposite effects on intracellular ROS and virus replication. Additionally, differentiated cells with intracellular virus replication showed reduced levels of surface markers compared to uninfected differentiated cells.
Dengue virus can infect human megakaryocytes leading to decreased platelet biogenesis. In this article, we report a study of Dengue replication in human K562 cells undergoing PMA-induced differentiation into megakaryocytes. PMA-induced differentiation in these cells recapitulates steps of megakaryopoiesis including gene activation, expression of CD41/61 and CD61 platelet surface markers and accumulation of intracellular reactive oxygen species (ROS). Our results show differentiating megakaryocyte cells to support higher viral replication without any apparent increase in virus entry. Further, Dengue replication suppresses the accumulation of ROS in differentiating cells, probably by only augmenting the activity of the transcription factor NFE2L2 without influencing the expression of the coding gene. Interestingly pharmacological modulation of NFE2L2 activity showed a simultaneous but opposite effect on intracellular ROS and virus replication suggesting the former to have an inhibitory effect on the later. Also cells that differentiated while supporting intracellular virus replication showed reduced level of surface markers compared to uninfected differentiated cells.
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