RESUMO
There is no specific chemotherapy approved for the treatment of pathogenic arenaviruses that cause severe hemorrhagic fever (HF) in the population of endemic regions in America and Africa. The present study reports the effects of the natural flavonoid quercetin (QUER) on the infection of A549 and Vero cells with Junín virus (JUNV), agent of the Argentine HF. By infectivity assays, a very effective dose-dependent reduction of JUNV multiplication was shown by cell pretreatment at 2-6 h prior to the infection at non-cytotoxic concentrations, with 50% effective concentration values in the range of 6.1-7.5 µg/mL. QUER was also active by post-infection treatment but with minor efficacy. Mechanistic studies indicated that QUER mainly affected the early steps of virus adsorption and internalization in the multiplication cycle of JUNV. Treatment with QUER blocked the phosphorylation of Akt without changes in the total protein expression, detected by Western blot, and the consequent perturbation of the PI3K/Akt pathway was also associated with the fluorescence redistribution from membrane to cytoplasm of TfR1, the cell receptor recognized by JUNV. Then, it appears that the cellular antiviral state, induced by QUER treatment, leads to the prevention of JUNV entry into the cell.
Assuntos
Infecções por Arenaviridae , Arenavirus , Chlorocebus aethiops , Animais , Quercetina/farmacologia , Flavonoides , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Células VeroRESUMO
Junín virus (JUNV), a member of the family Arenaviridae, is the etiological agent of the Argentine hemorrhagic fever, an endemic disease in the rural region of Argentina lacking a specific chemotherapy. Aryl hydrocarbon receptor (AHR) is expressed in several mammalian tissues and has been indicated as a sensor of ligands from variable sources and a modulator of the cell immune response. Interestingly, recent studies have suggested that the activation or depression of the AHR signaling pathway may play a role in the outcome of diverse human viral infections. In the present report, the effect of the pharmacological modulation of AHR on JUNV in vitro infection was analyzed. An initial microarray screening showed that the AHR pathway was overexpressed in JUNV-infected hepatic cells. Concomitantly, the infection of Vero and Huh-7 cells with the JUNV strains IV4454 and Candid#1 was significantly inhibited in a dose-dependent manner by treatment with CH223191, a specific AHR antagonist, as detected by infectivity assays, real-time RT-PCR and immunofluorescence detection of viral proteins. Furthermore, the pro-viral role of AHR in JUNV infection appears to be independent of the IFN-I pathway. Our findings support the promising perspectives of the pharmacological modulation of AHR as a potential target for the control of AHF.
Assuntos
Arenaviridae , Vírus Junin , Animais , Humanos , Argentina , Mamíferos , Receptores de Hidrocarboneto Arílico/genética , Transdução de Sinais , Replicação ViralRESUMO
El trabajo de investigación fue realizado en la gestión 2000, entre sep. y dic. con el objeto de determinar el mejor grado de corte y madurez de bananos para ofrecer productos de calidad en la comercialización. El lugar donde se realizó el trabajo fue en la Estación Experimental La Jota, considerando un diseño completamente aleatorio para los factores: Indice de cosecha, grado de madurez y maduración, y las variables de respuesta fueron: color, firmeza, relación pulpa y cáscara, sólidos solubles, pH y acidez. Los resultados reportaron el mejor grado de corte. Y los resultados de características a cosecha, en los diferentes grados de corte, hubo diferencias según la edad del racimo, para la maduración a través de dos días, para la FHIA 01, maduro a los 22 días a una edad de 12 semanas, a 17 días a una edad de 13 semanas y a 12 días a una edad de 14 semanas. Para la FHIA 18 maduro a los 18 días a una edad de 12 semanas, a 13 días a una edad de 13 semanas, a 9 días a una edad de 14 semanas y para Grand Naine, maduro a los 10 días a una edad de 12 semanas. Entre los cultivares se encontró diferencias en los grados de madures, para la firmeza, el pH y acidez, la FHIA 18 presentó mayor firmeza, el pH más bajo y más ácido que el resto de los otros cultivares, en relación pulpa y cascara, sólidos solubles fue Grand Naine que llego a tener mayor relación pulpa y cascara y solidos solubles que los otros cultivares.
