Matrix metalloproteinases in the pathogenesis of dengue viral disease: Involvement of immune system and newer therapeutic strategies

• Published in: Journal of medical virology 2021-08, Vol.93 (8), p.4629-4637
• Main Authors: Niranjan, Rituraj, Kishor, Sumitha, Kumar, Ashwani
• Format: Article
• Language: English
• Subjects: Antibodies; Biomedical materials; CCL3 protein; CCL4 protein; CD16 antigen; Cell activation; Cytokines; Dendritic cells; Dengue fever; dengue shock syndrome; dengue virus; Endothelium; Gelatinase A; Gelatinase B; immune cells in dengue fever; Immune system; Inflammation; Lymphocytes; Lymphocytes T; Macrophages; Matrix metalloproteinase; Matrix metalloproteinases; Metalloproteinase; Metastases; metrix metalloproteinases; MicroRNAs; miRNA; Monocyte chemoattractant protein 1; Monocytes; Osteosarcoma; Pathogenesis; Pathology; Proteolysis; Stromelysin 1; Tissue inhibitor of metalloproteinases; Tumor necrosis factor; Ulcerative colitis; Vector-borne diseases; Viral diseases; Virology; Viruses
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.26903

Globally, the burden due to dengue infection is increasing with a recent estimate of 96 million progressing to the disease every year. Dengue pathogenesis and the factors influencing it are not completely known. It is now widely speculated that there is an important role of matrix metalloproteinases (MMPs) in the initiation and progression of dengue pathogenesis; however, their exact roles are not fully understood. Overactivation of matrix metalloproteinases may contribute to the severity of dengue pathogenesis. Cytokines and various other mediators of inflammation interact with the vascular endothelium and matrix metalloproteinases may be one of the components among them. Extensive plasma leakage into tissue spaces may result in a shock. It is evident in the literature that MMP2 and MMP9 increase in dengue patients is correlated with the severity of the disease; however, the underlying mechanism is still unknown. Activation of innate cells and adaptive immune cells which include, B and T cells, macrophages or monocytes and dendritic cells also contribute to the dengue pathology. Newer therapeutic strategies include microRNAs, such as miR‐134 (targets MMP3 and MMP1) and MicroRNA‐320d, (targets MMP/TIMP proteolytic system). The use of antibodies‐based therapeutics like (Andecaliximab; anti‐matrix metalloproteinase‐9 antibody) is also suggested against MMPs in dengue. In this review, we summarize some recent developments associated with the involvement of immune cells and their mediators associated with the matrix metalloproteinases mediated dengue pathogenesis. We highlight that, there is still very little knowledge about the MMPs in dengue pathogenesis which needs attention and extensive investigations. Highlights 1. We describe that there is an important role of matrix metalloproteinases (MMPs) in the initiation and progression of dengue pathogenesis. 2. We highlight that over activation of matrix metalloproteinases may contribute to the severity of dengue pathogenesis. Notably, CD16+ monocytes infected with DENV have been reported to produce CCL2, CCL3, CCL4, IL‐1β, and TNF‐α in excessive amounts. 3. Cytokines and various other mediators of inflammation interact with the vascular endothelium and matrix metalloproteinases may be one of the components among them. 4. The details of MMP2 and MMP9 in the severity of the disease were analytically discussed. 5. Role of innate cells and adaptive immune cells which include, B and T cells, macrophages or monocytes