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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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.
Total Authors: 9
Document type: Journal article
Source: JOURNAL OF PROTEOME RESEARCH; v. 16, n. 4, p. 1542-1555, APR 2017.
Web of Science Citations: 6

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)

FAPESP's process: 09/01400-7 - Study of the interaction of NS4b of yellow fever virus and host cellular proteins
Grantee:Maurício Lacerda Nogueira
Support Opportunities: Regular Research Grants
FAPESP's process: 10/05043-1 - Characterization of the interaction of the NS5 protein of Yellow Fever with the human cellular protein eIF3L
Grantee:Ana Theresa Silveira de Morais
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)