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.
Highlights
Zika virus (ZIKV) was isolated for the first time in 1947 in the Zika forest, Uganda; a member of the Flaviviridae family, it is the etiologic agent of a disease with the same name, which is characterized as a self-limited infection where over 80% of the infected patients do not present any signs or symptoms (Duffy et al, 2009; Petersen et al, 2016)
Statistical analysis was performed by using orthogonal partial least squares discriminant analysis (OPLS-DA), based on mass spectral data obtained by the direct infusion of serum, using the results from RT-PCR to provide guidance and support in the establishment of the two studied groups
The rationale of mixing symptomatic patients and healthy individuals in the control group was a key feature of this study, as it is an ideal representation of the heterogeneity found in any given population in terms of clinical status
Summary
Zika virus (ZIKV) was isolated for the first time in 1947 in the Zika forest, Uganda; a member of the Flaviviridae family, it is the etiologic agent of a disease with the same name, which is characterized as a self-limited infection where over 80% of the infected patients do not present any signs or symptoms (Duffy et al, 2009; Petersen et al, 2016). ZIKV Metabolomics of Human Serum manifestations of the disease usually develop unspecific symptoms such as fever, conjunctivitis, skin rashes, arthralgia, macular rash, myalgia, migraine, and retro-orbital pain, among other symptoms that may be clinically associated with the common influenza virus, as well as other arboviruses such as dengue (DENV), oropouche (OROV) or chikungunya (CHIKV) (Duffy et al, 2009; Daumas et al, 2013; Pabbaraju et al, 2016; Paniz-Mondolfi et al, 2016) Because it was considered a relatively harmless infection up to 2014, ZIKV was not remarkably relevant in public health worldwide, remaining relatively unknown among people and even physicians. The recent possibility of ZIKV transmission sexually and via hemoderivatives (Musso et al, 2015; Center for Biologics Evaluation and Research, 2016; Fréour et al, 2016; Katz and Rossmann, 2016; Russell et al, 2016) has created a context in which understanding the pathophysiological mechanism of infection became vitally relevant to pave the way toward the development of effective therapies, and to prevent associated aggravations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
