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HCMV Induces Dysregulation of Glutamate Uptake and Transporter Expression in Human Fetal Astrocytes

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Abstract

Human cytomegalovirus (HCMV) infections are the leading cause of viral induced birth defects, affecting the central nervous system (CNS) primarily. Fetal CNS is especially vulnerable to CMV induced injury. As HCMV permissive cells, astrocytes are responsible for major glutamate transport and regulate extracellular levels of glutamate avoiding its accumulation which is implicated in neurodegenerative disorders. In this study, highly purified astrocytes isolated from human first trimester aborted fetal brain were infected with HCMV AD169, glutamate uptake function was detected by 3H labeling technic, and the expression level alterations of glutamate transporters (GLAST, GLT-1), glutamine synthetase (GS) and its activity were also investigated. Protein kinases C (PKC) inhibitor treatment was to identify whether PKC signalling involved in regulating glutamate uptake, protein expression of GLAST, GLT-1, GS and GS activity. Results indicated HCMV AD169 infection could modulate glutamate uptake, expression levels of GLAST, GLT-1, GS and it activity through PKC signalling, suggesting a great susceptibility of human fetal astrocytes to HCMV infection, which significantly alters the uptake and metabolism of an important excitatory amino acid, glutamate, may be a potential mechanism for HCMV associated neurological disease, and an effective therapeutic target in neural diseases.

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Acknowledgments

This work was supported by the National Natural Science Fund (No. 81471958), National Natural Science Fund (No. 81070501), the Specialized Research Fund for Doctoral Program of Higher Education (No. 20093706110001), and Qingdao University medical innovation team of young teachers training project (No. 600201304). The authors thank the Pasteur Institute in France for kindly providing us the HCMV AD169. They also thank the Department of Gynecology and Obstetrics of the Affiliated Hospital of Qingdao University School of Medicine for providing human fetus preparation. Useful suggestions and critical revision given by Dr. Guo-ying Wang of Qingdao University are also acknowledged.

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There are no conflicts of interest.

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The authors ensured that all procedures were performed in compliance with relevant laws and institutional guidelines and that the Qingdao University Human Investigation Committee has approved them.

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Authors and Affiliations

  1. Department of Microbiology, Key Laboratory of Medicine and Biotechnology of Qingdao, Qingdao University School of Medicine, Qingdao, 266071, Shandong, China

    Li Zhang, Ling Li, Bin Wang, Dong-Meng Qian, Xu-Xia Song & Ming Hu

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  1. Li Zhang
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  2. Ling Li
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  3. Bin Wang
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Correspondence to Bin Wang.

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Zhang, L., Li, L., Wang, B. et al. HCMV Induces Dysregulation of Glutamate Uptake and Transporter Expression in Human Fetal Astrocytes. Neurochem Res 39, 2407–2418 (2014). https://doi.org/10.1007/s11064-014-1445-5

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  • DOI: https://doi.org/10.1007/s11064-014-1445-5

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