Abstract
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.
Highlights
Dengue virus (DENV) infection causes a self-limiting acute febrile illness with the potential to turn fatal
In this report we show that DENV replicates better in megakaryocytes and virus infection interferes with accumulation of reactive oxygen species (ROS), thereby potentially inhibiting platelet biogenesis
Real-time PCR based investigation, into the differential expression of genes selected from a study of published literature, showed the expression of certain unique MK-specific genes to be upregulated by Phorbol12 myristate-13 (PMA) but not by sodium butyrate (Li et al, 2008)
Summary
Dengue virus (DENV) infection causes a self-limiting acute febrile illness with the potential to turn fatal. Independent of disease severity, DENV infection causes thrombocytopenia to a lesser or greater extent with severe patients exhibiting acute drop in platelet level along with leakage of fluid from the blood vessels (Martina et al, 2009). Multiple mechanisms have been suggested to contribute to thrombocytopenia including attenuated platelet biogenesis and increased platelet decay through either direct virus interaction or upon binding of anti-platelet antibodies (Fang et al, 2013; de Azeredo et al, 2015; Simon et al, 2015; Ojha et al, 2017, 2019). Platelets in the blood are produced from specialized bone-marrow resident cells called Megakaryocytes (MKs), at a steady rate of biogenesis (about 1 × 109/day) and with an average life of 7 days in humans (Patel et al, 2005). MKs are generated from bi-potential Megakaryocyte-Erythrocyte progenitor (MEP) cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
