www.proteomics-journal.com Page 1 Proteomics Received: 03 05, 2016; Revised: 06 15, 2016; Accepted: 06 16, 2016 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/pmic.201600126. This article is protected by copyright. All rights reserved. Comparative proteome analysis reveals that blood and sugar meals induce differential protein expression in Aedes aegypti female heads Alessandra T. Nunes 1 , Nathalia F. Brito 1, Daniele S. Oliveira 1 , Gabriel D. T. Araujo 2 , Fabio Cesar S. Nogueira 2 , Gilberto B. Domont 2 , Monica F. Moreira 1,4 , Leandro M. Moreira 3 , Marcia R. Soares 1 , Ana C. A. Melo 1,4* 1 Universidade Federal do Rio de Janeiro, Instituto de Química, 21941-909, Rio de Janeiro, Brazil, 2 Proteomics Unit, Federal University of Rio de Janeiro, Chemistry Institute, 21941-909, Rio de Janeiro, Brazil, 3 Universidade Federal de Ouro Preto, Instituto de Ciências Exatas e Biológicas, 35400- 000, Ouro Preto, Brazil, 4 Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, Brazil. * Corresponding author anamelo@iq.ufrj.br Abstract Aedes aegypti females ingest sugar or blood to obtain the nutrients needed to maintain cellular homeostasis. During human blood ingestion, female mosquitoes may transmit different viruses such as dengue, yellow fever and, more recently, zika and chikungunya. Here, we report changes in protein expression in heads of adult female Ae. aegypti mosquitoes in response to the ingestion of blood or sugar. Proteins extracted from heads of Ae. aegypti fed exclusively on blood (BF) or sugar (SF) were trypsin hydrolyzed (off-gel) and analyzed by reverse-phase nano-liquid chromatography coupled with hybrid mass spectrometry. A total of 1,139 proteins were identified in female heads, representing 7.4% of the predicted proteins in Ae. aegypti genome (total = 15,419 active genes). Gene ontology annotation and categories showed that, in this insect, the head was rich in proteins involved in the metabolic process, proton transport, organelle, macromolecular complex, structural molecule activity,