Relationship between MMP Expression and Virulence of Dengue Virus Type-2 in Infected Mosquito and Mammalian Cells

Abstract

SUMMARY:Dengue virus infections are mostly asymptomatic but can produce a mild, self-limiting acute febrile illness, dengue fever, or a life threatening severe illness, dengue hemorrhagic fever. Dengue hemorrhagic fever is associated with increased vascular permeability partly as a result of elevated levels of matrix metalloproteinases (MMPs). We characterized MMP-2 and MMP-9 production in mosquito and mammalian cells after infection with three strains of dengue virus type-2 (D2-) ranging in virulence: 16681, the prototype New Guinea C (NGC), and PDK-53 vaccine strain. These strains were used to test variations in viral properties in vaccine candidates and confirm the production of MMP as a possible marker for virulence. A zymogram gelatinolytic activity assay was used to assess MMP-2 and MMP-9 production. We found that dengue-infected mosquito and mammalian cell lines had unique MMP-2 and MMP-9 production patterns depending on the virulence of the infecting dengue strain and the duration infection. MMP levels were highest after infection with the most virulent strain D2-16681, followed by the prototype NGC strain, in both cell lines. The MMP levels appeared to correspond with the relative amounts of infectious virions produced later in infection. Our findings improve our understanding of dengue pathogenesis and may facilitate the selection of markers to further the development of dengue vaccines.

Transcriptome comparison of dengue-susceptible and -resistant field derived strains of Colombian Aedes aegypti using RNA-sequencing

“…In humans, increased MMP activity is associated with increased pathogenicity, as MMPs assist in breaking down the basal lamina of tissues, allowing for subsequent viral entry and replication, often resulting in increased vascular leakage. 21 In mosquitoes, MMPS have been implicated in extracellular matrix remodelling, potentially allowing virions to pass through an altered basal lamina. 22 MMPs also have been annotated as anti-viral, acting as apoptotic effectors in the important anti-viral JAK-STAT pathway.…”

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

“…92 There are still very limited studies that showed the linkage of the immune system with matrix metalloproteinases. 93 However, some studies have shown that there is a role of immune cells and their mediators in the regulation of MMPs in dengue viral disease especially DSS. We, for the first time, have shown that there is a very important role of monocytes in mediated MMPs expression in response to dengue viral NS-1 protein.…”

“…There are still very limited studies that showed the linkage of the immune system with matrix metalloproteinases 93 . However, some studies have shown that there is a role of immune cells and their mediators in the regulation of MMPs in dengue viral disease especially DSS.…”