RESUMEN
In this study, we demonstrate the synthesis of carbonized nanogels (CNGs) from an amino acid (lysine hydrochloride) using a simple pyrolysis method, resulting in effective viral inhibition properties against infectious bronchitis virus (IBV). The viral inhibition of CNGs was studied using both in vitro (bovine ephemeral fever virus (BEFV) and pseudorabies virus (PRV)) and in ovo (IBV) models, which indicated that the CNGs were able to prevent virus attachment on the cell membrane and penetration into the cell. A very low concentration of 30 µg mL-1 was found to be effective (>98% inhibition) in IBV-infected chicken embryos. The hatching rate and pathology of IBV-infected chicken embryos were greatly improved in the presence of CNGs. CNGs with distinctive virus-neutralizing activities show great potential as a virostatic agent to prevent the spread of avian viruses and to alleviate the pathology of infected avian species.
Asunto(s)
Antivirales/farmacología , Infecciones por Coronavirus/tratamiento farmacológico , Virus de la Bronquitis Infecciosa/efectos de los fármacos , Lisina/farmacología , Nanogeles/administración & dosificación , Sustancias Protectoras/farmacología , Animales , Línea Celular , Pollos/virología , Chlorocebus aethiops , Infecciones por Coronavirus/virología , Cricetinae , Virus de la Fiebre Efímera Bovina/efectos de los fármacos , Femenino , Herpesvirus Suido 1/efectos de los fármacos , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/virología , Ratas , Ratas Sprague-Dawley , Células Vero , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
Bovine ephemeral fever (BEF) is caused by the arthropod-borne bovine ephemeral fever virus (BEFV), which is a member of the family Rhabdoviridae and the genus Ephemerovirus. BEFV causes an acute febrile infection in cattle and water buffalo. In this study, a recombinant Newcastle disease virus (NDV) expressing the glycoprotein (G) of BEFV (rL-BEFV-G) was constructed, and its biological characteristics in vitro and in vivo, pathogenicity, and immune response in mice and cattle were evaluated. BEFV G enabled NDV to spread from cell to cell. rL-BEFV-G remained nonvirulent in poultry and mice compared with vector LaSota virus. rL-BEFV-G triggered a high titer of neutralizing antibodies against BEFV in mice and cattle. These results suggest that rL-BEFV-G might be a suitable candidate vaccine against BEF.
Asunto(s)
Anticuerpos Neutralizantes/biosíntesis , Anticuerpos Antivirales/biosíntesis , Virus de la Fiebre Efímera Bovina/genética , Fiebre Efímera/prevención & control , Virus de la Enfermedad de Newcastle/genética , Vacunas Virales/genética , Animales , Bovinos , Embrión de Pollo , Cricetinae , Perros , Fiebre Efímera/inmunología , Fiebre Efímera/virología , Virus de la Fiebre Efímera Bovina/efectos de los fármacos , Virus de la Fiebre Efímera Bovina/inmunología , Células Epiteliales/virología , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/inmunología , Glicoproteínas/administración & dosificación , Glicoproteínas/genética , Glicoproteínas/inmunología , Inmunización , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos BALB C , Virus de la Enfermedad de Newcastle/inmunología , Virus Reordenados/genética , Virus Reordenados/inmunología , Vacunas Sintéticas , Proteínas Virales/administración & dosificación , Proteínas Virales/genética , Proteínas Virales/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/inmunologíaRESUMEN
Recent study in our laboratory has demonstrated that BEFV-induced autophagy via activation of the PI3K/Akt/NF-κB and Src/JNK pathways and suppression of the PI3K-AKt-mTORC1 pathway is beneficial for virus replication. In the current study, we found that both aspirin and 5-aminoimidazole-4-carboxamide-1-ß-riboside (AICAR) siginificantly attenuated virus replication by inhibiting BEFV-induced autophagy via suppressing the BEFV-activated PI3K/Akt/NF-κB and Src/JNK pathways as well as inducing reversion of the BEFV-suppressed PI3K-Akt-mTORC1 pathway. AICAR reversed the BEFV-activated PI3K/Akt/NF-κB and Src/JNK pathways at the early to late stages of infection and induced reversion of the BEFV-suppressed PI3K-AKt-mTORC1 pathway at the late stage of infection. Our findings reveal that inhibition of BEFV-induced autophagy by AICAR is independent of AMPK. Furthermore, we found that AICAR transcriptionally downregulates the ATG related genes ULK1, Beclin 1, and LC3 and enhances Atg7 degradation by the proteasome pathway. Aspirin suppresses virus replication by inhibiting BEFV-induced autophagy. It directly suppressed the NF-κB pathway and reversed the BEFV-activated Src/JNK pathway at the early stage of infection and reversed the BEFV-suppressed PI3K/Akt/mTOR pathway at the late stage of infection. The current study provides mechanistic insights into the effects of aspirin and AICAR on BEFV replication through suppression of BEFV-induced autophagy.