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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.)

The first characterization of a cystatin and a cathepsin L-like peptidase from Aedes aegypti and their possible role in DENV infection by the modulation of apoptosis

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Oliveira, Felipe A. A. [1] ; Buri, Marcus V. [1] ; Rodriguez, Boris L. [1] ; Costa-da-Silva, Andre L. [2] ; Araujo, Helena R. C. [2] ; Capurro, Margareth L. [2] ; Lu, Stephen [1] ; Tanaka, Aparecida S. [1]
Total Authors: 8
[1] Univ Fed Sao Paulo UNIFESP, Dept Biochem, Escola Paulista Med, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: International Journal of Biological Macromolecules; v. 146, p. 141-149, MAR 1 2020.
Web of Science Citations: 0

Recently, a salivary gland transcriptome study demonstrated that the transcripts of a putative cystatin gene (SeqID AAEL013287; Aacystatins) from Aedes aegypti were increased in DENV2-infected mosquitoes and that silencing of the Aacystatin gene resulted in an increase in DENV titres. In this work, Aacystatin was biochemically characterized; the purified recombinant inhibitor was able to inhibit typical cysteine proteases with a Ki in the nM range. Pulldown assays using Aag2 cell extracts identified a cathepsin L-like peptidase (AaCatL) as a possible target of Aacystatin. Purified recombinant AaCatL had an optimal pH of 5.0 and displayed a preference for Leu, Val and Phe residues at P2, which is common for other cathepsin L-like peptidases. Transcription analysis of Aacystatin and AaCatL in the salivary glands and midgut of DENV2-infected mosquitoes revealed a negative correlation between DENV2 titres and levels of the inhibitor and peptidase, suggesting their involvement in DENV2-mosquito interactions. Considering that apoptosis may play an important role during viral infections, the possible involvement of Aacystatin in staurosporine-induced apoptosis in Aag2 cells was investigated; the results showed higher expression of the inhibitor in treated cells; moreover, pre incubation with rAacystatin was able to increase Aag2 cell viability. (C) 2019 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 13/16609-4 - Aedes aegypti sex conversion by transgenesis
Grantee:Helena Rocha Corrêa de Araújo
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 12/03657-8 - Inhibitor and proteases of ectoparasites: relationship of structure-function and identification of the role of these molecules in the interaction of diseases vector e their etiological agents
Grantee:Aparecida Sadae Tanaka
Support type: Research Projects - Thematic Grants