Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Program in Structural Biology and Biochemistry, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Transfusion. 2022 May;62(5):1045-1064. doi: 10.1111/trf.16851. Epub 2022 Mar 14.
Diseases caused by arthropod-borne viruses remain a burden to global health; in particular, Zika virus (ZIKV) has been reported in 87 countries and territories. In healthy blood donors, ZIKV RNA can be detected in red blood cells (RBCs) months after infection, clearance of detectable nucleic acid in plasma, and seroconversion. However, little information is available on the impact of ZIKV infection to metabolism.
We applied mass spectrometry-based metabolomics and lipidomics approaches to investigate the impact of ZIKV infection on RBCs over the course of infection. ZIKV-infected blood donors (n = 25) were identified through molecular and serologic methods, which included nucleic acid amplification testing and real-time polymerase chain reaction (PCR) for detection of ZIKV RNA and enzyme-linked immunosorbent assay (ELISA) for detection of flavivirus-specific IgM and IgG.
In ZIKV RNA-positive donors, we observed lower glucose and lactate levels, and higher levels of ribose phosphate, suggestive of the activation of the pentose phosphate pathway. The top pathways altered in RBCs from ZIKV-IgM-positive donors include amino acid metabolism and biosynthesis, fatty acid metabolism and biosynthesis, linoleic acid and arachidonate metabolism and glutathione metabolism. RBCs from ZIKV-infected donors had increased levels of early glycolytic metabolites, and higher levels of metabolites of the pentose phosphate pathway. Alterations in acyl-carnitine and fatty acid metabolism are consistent with impaired membrane lipid homeostasis in RBCs from ZIKV IgM positive donors.
RBC from healthy blood donors who had been infected by ZIKV are characterized by long-lasting metabolic alterations even months after infection has resolved.
虫媒病毒引起的疾病仍然是全球健康的负担；特别是寨卡病毒（ZIKV）已在 87 个国家和地区报告。在健康的献血者中，ZIKV RNA 可在感染后数月于红细胞（RBC）中检测到，血浆中可检测到的核酸清除和血清转化。然而，关于 ZIKV 感染对代谢的影响的信息很少。
我们应用基于质谱的代谢组学和脂质组学方法来研究 ZIKV 感染对 RBC 的影响。通过分子和血清学方法鉴定 ZIKV 感染的献血者（n=25），包括核酸扩增检测和实时聚合酶链反应（PCR）检测 ZIKV RNA 和酶联免疫吸附测定（ELISA）检测黄病毒特异性 IgM 和 IgG。
在 ZIKV RNA 阳性供体中，我们观察到葡萄糖和乳酸水平较低，核糖磷酸水平较高，提示戊糖磷酸途径被激活。ZIKV-IgM 阳性供体 RBC 中改变最明显的途径包括氨基酸代谢和生物合成、脂肪酸代谢和生物合成、亚油酸和花生四烯酸代谢以及谷胱甘肽代谢。ZIKV 感染供体的 RBC 具有更高水平的早期糖酵解代谢物和戊糖磷酸途径的代谢物。酰基肉碱和脂肪酸代谢的改变与 RBC 中膜脂质稳态受损一致，ZIKV IgM 阳性供体的 RBC 中存在这种情况。
即使在感染得到解决后的数月，感染 ZIKV 的健康献血者的 RBC 仍具有持久的代谢改变。
