AUTHOR=Melo Carlos Fernando O. R. , Delafiori Jeany , de Oliveira Diogo N. , Guerreiro Tatiane M. , Esteves Cibele Z. , Lima Estela de O. , Pando-Robles Victoria , Catharino Rodrigo R. , the Zika-Unicamp Network , Milanez Guilherme P. , do Nascimento Gabriela M. , Freitas André R. R. , Angerami Rodrigo , Costa Fábio T. Maranhão , Arns Clarice W. , Resende Mariangela R. , Amaral Eliana , Junior Renato P. , Ribeiro-do-Valle Carolina C. , Milanez Helaine , Moretti Maria L. , Proenca-Modena Jose L. , Pastore Glaucia M. , Fertrin Kleber Y. , Garcia Márcia T. , Calil Roseli , Júnior João R. B. , Lajos Giuliane J. , Costa Maria L. , da Silva Marcos T. N. , Altemani Albina , Coan Ana C. , Colella-Santos Maria F. , von Zuben Andrea P. B. , Vinolo Marco A. R. , de Paula Rosemeire F. de O. , Judice Carla C. , Leite Juliana A. , Caserta Leonardo C. , de Moraes Ana P. , Barnabé Ana C. S. , da Soledade Ana L. R. , Teixeira Daniel A. T. , de Morais Évellyn R. , Santos Felipe R. TITLE=Serum Metabolic Alterations upon Zika Infection JOURNAL=Frontiers in Microbiology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.01954 DOI=10.3389/fmicb.2017.01954 ISSN=1664-302X ABSTRACT=

Zika virus (ZIKV) infection has recently emerged as a major concern worldwide due to its strong association with nervous system malformation (microcephaly) of fetuses in pregnant women infected by the virus. Signs and symptoms of ZIKV infection are often mistaken with other common viral infections. Since transmission may occur through biological fluids exchange and coitus, in addition to mosquito bite, this condition is an important infectious disease. Thus, understanding the mechanism of viral infection has become an important research focus, as well as providing potential targets for assertive clinical diagnosis and quality screening for hemoderivatives. Within this context, the present work analyzed blood plasma from 79 subjects, divided as a control group and a ZIKV-infected group. Samples underwent direct-infusion mass spectrometry and statistical analysis, where eight markers related to the pathophysiological process of ZIKV infection were elected and characterized. Among these, Angiotensin (1-7) and Angiotensin I were upregulated under infection, showing an attempt to induce autophagy of the infected cells. However, this finding is concerning about hypertensive individuals under treatment with inhibitors of the Renin-Angiotensin System (RAS), which could reduce this response against the virus and exacerbate the symptoms of the infection. Moreover, one of the most abundant glycosphingolipids in the nervous tissue, Ganglioside GM2, was also elected in the present study as an infection biomarker. Considered an important pathogen receptor at membrane's outer layer, this finding represents the importance of gangliosides for ZIKV infection and its association with brain tropism. Furthermore, a series of phosphatidylinositols were also identified as biomarkers, implying a significant role of the PI3K-AKT-mTOR Pathway in this mechanism. Finally, these pathways may also be understood as potential targets to be considered in pharmacological intervention studies on ZIKV infection management.