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

Abstract

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.

Dengue fever ophthalmic manifestations: A review and update

“…It is evident that increased levels of MMP2 and MMP9 in patients with dengue are correlated with disease severity, and excessive MMP activity may play a role in keratitis pathogenesis. This results in the release of cytokines with vasoactive and procoagulant properties in response to immunological activation 60 …”

“…This results in the release of cytokines with vasoactive and procoagulant properties in response to immunological activation. 60 Several case reports have described a shallow anterior chamber and angle-closure glaucoma in patients with DF, in which ciliary congestion and choroidal effusions may play important roles. 40 The mechanisms of angle closure consist of forward movement of the lens-iris complex, which results in a reduction in the anterior chamber depth.…”

The Role of Matrix Metalloproteinase in Infectious Diseases

“…In particular, it has been reported that MMP-2 and MMP-9 are increased by ZIKV as well as DENV and JEV infection to induce vascular leakage as well as increase in BBB permeability [101,102,103]. In a recent review on the role of MMPs in the pathogenesis of DENV, it was also noted that there is a correlation between the disease severity caused by DENV infection and MMP-2 and MMP-9 [104]. In the study of the association of MMPs with various diseases such as vascular disease, lung disease, and cancer, MMP-2 and MMP-9 have been heavily studied due to their broad substrate specificity.…”

The role and function of secretory protein MMP3 in cervical cancer

“…Therefore, it is a greatly clinical implication to investigate new therapeutic approaches and CCA-related molecular mechanisms. Matrix metalloproteinase3 (MMP3) is one of the major members of the MMPs family [3]. The human MMP3 gene is localized in the chromosome 11q22.3 region and is approximately 1.8 kb.…”