In vitro antiviral activity of lambda carrageenan against DENV infection of human myeloid cell in absence or presence of antibodies

ANA C. CARRO; LUANA É PICCINI; ELSA B. DAMONTE

Porto

Conferencia; 31st International Conference on Antiviral Research; 2018

Dengue is the most prevalent arthropode-borne viral human disease in tropical and subtropical regions, caused by four dengue virus (DENV) serotypes. In spite of the increasing global incidence, no specific antiviral therapy is available. Cells of the mononuclear phagocyte lineage are the main targets either for primary or secondary antibody (Ab)-mediated DENV infection, usually associated to severe forms of disease. Since virus entry may be a convenient therapeutic alternative, and sulfated polysaccharides (PS), such as λ carrageenan, mimics heparan sulfate, one of the receptors used by DENV to establish infection in mammalian cells and exhibit antiviral activity during the early stages of the multiplication cycle of different enveloped viruses. So, this study aimed to investigate the antiviral activity of λ carrageenan on the infection of DENV, in the presence and absence of antibodies, in monocytic cells U937 and erythroleukemic K562. Therefore, the cytotoxic concentration of the λ carrageenan was determined by tripan blue exclusion method, and antiviral activity was studied by viral yield inhibition, and its mechanism of action was analyzed by time addition of the compound at different times of the infection. λ carrageenan was non cytotoxic in all range of concentrations evaluated, and produces a strong inhibition of DENV multiplication in antibody absence, with an effectiveness concentration under 1.25 µg/ml for all four serotypes. The compound inhibits the viral adsorption and internalization, and no effect was seen when λ carrageenan was added 10 h post-infection. λ carrageenan also presents antiviral activity, when K562 cells was infected with DENV-2 or DENV-3 in antibody presence, in contrast, neither activity was excerted when U937 cells were infected with the mixtures DENV-2-2H2 and DENV-3-2H2. When the mechanism of action was evaluated in the system K562-DENV-2-2H2, the adsorption and internalization were the steps inhibited. Furthermore, the comparison confirms that diverse viral and cellular factors were involved and should be considered for evaluation of safe antiviral agents reactive against all DENV serotypes.