Untargeted Metabolomics Insights into Newborns with Congenital Zika Infection

Abstract

Zika virus (ZIKV), an emerging virus belonging to the Flaviviridae family, causes severe neurological clinical complications and has been associated with Guillain-Barré syndrome, fetal abnormalities known collectively as congenital Zika syndrome, and microcephaly. Studies have shown that ZIKV infection can alter cellular metabolism, directly affecting neural development. Brain growth requires controlled cellular metabolism, which is essential for cell proliferation and maturation. However, little is known regarding the metabolic profile of ZIKV-infected newborns and possible associations related to microcephaly. Furthering the understanding surrounding underlying mechanisms is essential to developing personalized treatments for affected individuals. Thus, metabolomics, the study of the metabolites produced by or modified in an organism, constitutes a valuable approach in the study of complex diseases. Here, 26 serum samples from ZIKV-positive newborns with or without microcephaly, as well as controls, were analyzed using an untargeted metabolomics approach involving gas chromatography–mass spectrometry (GC-MS). Significant alterations in essential and non-essential amino acids, as well as carbohydrates (including aldohexoses, such as glucose or mannose) and their derivatives (urea and pyruvic acid), were observed in the metabolic profiles analyzed. Our results provide insight into relevant metabolic processes in patients with ZIKV and microcephaly.

Senecavirus A- and Non-Infected Cells at Early Stage of Infection: Comparative Metabolomic Profiles

“…In the virological field, the first metabolomics study was reported in 2006, and analyzed over sixty metabolites during human cytomegalovirus infection (Munger et al, 2006). Since then, a variety of viruses have been demonstrated to alter multiple metabolic pathways in cells, like glycolysis and fatty acid synthesis, and have expanded the number of cellular metabolites (Birungi et al, 2010;Ritter et al, 2010;Hollenbaugh et al, 2011;Delgado et al, 2012;Sanchez et al, 2017;Tian et al, 2019;Li et al, 2021;Nunes et al, 2021;Pant et al, 2021;Wang et al, 2021). We have constructed a wild-type SVA (CH-LX-01-2016) using reverse genetics (Liu et al, 2021a), and more recently have revealed a proteomic profile of BSR-T7/5 cells inoculated with this virus at 12 hpi (Liu et al, 2021b).…”

Amniotic fluid metabolomics identifies impairment of glycerophospholipid and amino acid metabolism during congenital Zika syndrome development

“…Previous reports of serine and proline deficiencies were associated with neurodegenerative disorders and intrauterine growth retardation [41]. ZIKV studies reported amino acid metabolism downregulation in the brain of ZIKV‐infected mice embryos [42], and specifically the serine metabolism dysregulation in ZIKV‐infected newborn serum [43]. Finally, a genome‐scale metabolic stoichiometric model determined that CHIKV, DENV, and ZIKV viruses cause a negative regulation of serine metabolism [44].…”

Metabolomics in the Research of Viral Infectious Disease Mechanisms

“…For instance, a rise in phosphatidylethanolamine (PE) has been observed in Zika virus-infected patients [11] . Levels of glucose or mannose are decreased, and significant alterations have been made to the metabolic pathway associated with Nicotinamide adenine dinucleotide (NAD+) [12,13] . The metabolic pathway associated with Nicotinamide adenine dinucleotide (NAD+) is significantly altered.…”