title: Differential inhibition of dengue virus infection in mammalian and mosquito cells by iota-carrageenan.
abstract: The antiviral activity against dengue virus-2 (DENV-2) of carrageenans reported here has shown a differential susceptibility of C6/36 HT and Vero cells, taken as models of mosquito and mammalian cells, depending on the structural class of polysaccharides: all polysaccharides blocked DENV-2 infection in monkey Vero cells, but only iota-carrageenans were virus inhibitors in mosquito cells. However, iota-carrageenans were less effective in mosquito cells in comparison with mammalian cells with effective concentration 50 % (EC(50)) values in C6/36 HT cells 4.9-17.5-fold higher than in Vero cells, as determined by virus yield reduction assay. The mode of action of iota-carrageenan in both cell types was strikingly different: in Vero cells the inhibitory activity was exerted only at the initiation of the cycle, affecting virion binding, whereas in mosquito cells DENV-2 adsorption was not affected and comparable levels of inhibition were obtained if the compound was added to cells together with the virus, after 8 h of infection or by cell pre-treatment before infection. Furthermore, iota-carrageenans induced a subtle alteration in mosquito cells, detected by cell proliferation and protein synthesis analyses, suggesting that a probable cellular target may be responsible for the refractory state of mosquito cells to DENV-2 infection produced by this class of polysulfates. The failure of iota-carrageenan to block DENV-2 adsorption to mosquito cells appeared to be related to the low presence of adequate heparan sulfate (HS) in C6/36 HT cell surface and is indicative of a differential participation of HS residues for DENV-2 entry in both types of cells.
authors.affiliation: Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Talarico
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, PO Box 19046, Curitiba, Paraná, Brazil.
authors.forename: Miguel D
authors.initials: MD
authors.lastname: Noseda
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, PO Box 19046, Curitiba, Paraná, Brazil.
authors.forename: Diogo R B
authors.initials: DRB
authors.lastname: Ducatti
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, PO Box 19046, Curitiba, Paraná, Brazil.
authors.forename: Maria E R
authors.initials: MER
authors.lastname: Duarte
authors.affiliation: Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina.
authors.forename: Elsa B
authors.initials: EB
authors.lastname: Damonte
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D009033:Culicidae; D003715:Dengue / Q000821:virology; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D002351:Carrageenan