ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Microbes and Innate Immunity
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1632634
This article is part of the Research TopicEmerging Mechanisms of Host-Pathogen Interactions and immune responsesView all 9 articles
Effects of dengue virus type-2 serotype (DENV-2) on expression profile of matrix metalloproteinases in THP-1, monocytes cells and their roles in endothelial dysfunctions; protective effect of atorvastatin
Provisionally accepted
Rituraj Niranjan1*
Pitchavel Vidhyapriya2Vyshali Murugasamy2
Muthukumaravel Subramanian2
Dr Ashwani Kumar2- 1ICMR - National Institute of Research in Tribal Health, Jabalpur, India
- 2ICMR - Vector Control Research Centre, Indira Nagar, India
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Dengue viral fever is one of the most important arboviral infections, particularly in tropical and subtropical regions. In dengue infection, monocytes mediated matrix metalloproteases are speculated to be implicated in tissue damage and vascular leakage, however, the exact mechanisms are largely unknown. In the present study, we investigated the expressions profiles of MMPs in primary monocytes and in, THP-1 cells infected with all dengue virus serotypes. The mechanism of MMPs mediated anti-viral effect of atorvastatin was also investigated in detail on dengue virus induced expressions profiles of mRNA and VEGF. We found elevated mRNA expressions profiles of, MMP-2, MMP-9 and MMP-14 in DENV-infected THP-1 cells compared to uninfected control group. Interestingly, these upregulated expressions of MMPs were reversed by atorvastatin. The similar patterns of mRNA expressions were also observed of MMPs and VEGF members in NS1 injected mice. The atorvastatin downregulated MMPs and VEGF expressions in this NS1 injected mice model. Next, to proof the role of immune cells in causing endothelial dysfunctions, secretome obtained from dengue virus-induced monocytes was exposed to endothelial cells. Interestingly, this secretome, elevated expression of pro-apoptotic and angiogenic markers like caspases, angiopoietins, VEGF and their receptor genes in endothelial (HUVEC) cells. These changes were reversed by atorvastatin in dose dependent manners. Furthermore, the mechanistic roles of MMP-9 in causing apoptosis and angiogenesis in endothelial cells was established. Thus, we suggested that the DENV-2 might cause monocytes mediated angiogenesis and apoptosis making endothelial dysfunctions which may resemble the mechanism of pathogenesis of dengue shock syndrome (DHF/DSS). Additionally, our finding shows that the atorvastatin has a MMPs inhibitory potential against dengue, which may be adopted in clinical trials against severe dengue viral disease. The current findings are interesting however, further studies may be needed to adopt the current findings in future.
Keywords: DENV, dengue virus, VEGF-D, Vascular endothelial growth factor-D, MMPs, matrix metalloproteinases, HDL, high-density lipoprotein, VEGF-C, Vascular endothelial growth factor-C, DHF, Dengue Haemorrhagic Fever, NS, non-structural protein, Dengue virus, matrix metalloproteinases (MMPs), apoptosis, and angiogenesis
Received: 21 May 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Niranjan, Vidhyapriya, Murugasamy, Subramanian and Kumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rituraj Niranjan, ICMR - National Institute of Research in Tribal Health, Jabalpur, India
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