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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication

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Autor(es):
Vidotto, Alessandra ; Morais, Ana T. S. ; Ribeiro, Milene R. ; Pacca, Carolina C. ; Terzian, Ana C. B. ; Gil, Laura H. V. G. ; Mohana-Borges, Ronaldo ; Gallay, Philippe ; Nogueira, Mauricio L.
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF PROTEOME RESEARCH; v. 16, n. 4, p. 1542-1555, APR 2017.
Citações Web of Science: 5
Resumo

Yellow fever virus (YFV) replication is highly dependent on host cell factors. YFV NS4B is reported to be involved in viral replication and immune evasion. Here interactions between NS4B and human proteins were determined using a GST pull-down assay and analyzed using 1-DE and LC-MS/MS. We present a total of 207 proteins confirmed using Scaffold 3 Software. Cyclophilin A (CypA), a protein that has been shown to be necessary for the positive regulation of flavivirus replication, was identified as a possible NS4B partner. 59 proteins were found to be significantly increased when compared with a negative control, and CypA exhibited the greatest difference, with a 22-fold change. Fisher's exact test was significant for 58 proteins, and the p value of CypA was the most significant (0.000000019). The Ingenuity Systems software identified 16 pathways, and this analysis indicated sirolimus, an mTOR pathway inhibitor, as a potential inhibitor of CypA. Immunofluorescence and viral plaque assays showed a significant reduction in YFV replication using sirolimus and cyclosporine A (CsA) as inhibitors. Furthermore, YFV replication was strongly inhibited in treated with both inhibitors using reporter BHK-21-rep-YFV17DLucNeolres cells. Taken together, these data suggest that CypA-NS4B interaction regulates YFV replication. Finally, we present the first evidence that YFV inhibition may depend on NS4B-CypA interaction. (AU)

Processo FAPESP: 09/01400-7 - Estudo das interações entre a proteína NS4B do vírus da febre amarela e proteínas celulares
Beneficiário:Maurício Lacerda Nogueira
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 10/05043-1 - Caracterização da interação entre proteínas não estruturais do vírus da Febre Amarela e eIF3L
Beneficiário:Ana Theresa Silveira de Morais
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 04/14846-0 - Rede de proteoma do estado de São Paulo
Beneficiário:Fabio Cesar Gozzo
Linha de fomento: Auxílio à Pesquisa - Programa GENOMA