title: Relationship between MMP Expression and Virulence of Dengue Virus Type-2 in Infected Mosquito and Mammalian Cells.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University.
authors.forename: Pornsawan
authors.initials: P
authors.lastname: Leaungwutiwong
authors.forename: James F
authors.initials: JF
authors.lastname: Kelley
authors.forename: Aucha
authors.initials: A
authors.lastname: Sachair
authors.forename: Akanitt
authors.initials: A
authors.lastname: Jittmittraphap
authors.forename: Natthanej
authors.initials: N
authors.lastname: Luplertlop
mesh_terms: D000818:Animals; D002460:Cell Line; D009033:Culicidae; D003716:Dengue Virus / Q000254:growth & development*; D004586:Electrophoresis; D005780:Gelatin / Q000378:metabolism; D006868:Hydrolysis; D008253:Macaca mulatta; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D019562:Viral Load; D014774:Virulence
chemical_list: D005780:Gelatin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9