Human herpesvirus 6 (HHV-6) induces dysregulation of glutamate uptake and transporter expression in astrocytes
| Autor: | Elizabeth Williams, Steven Jacobson, Julie Fotheringham, Nahid Akhyani |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Gene Expression Regulation
Viral viruses Herpesvirus 6 Human Immunology Central nervous system Neuroscience (miscellaneous) Glutamic Acid Astrocytoma Virus Replication Immediate-Early Proteins Glutamate Plasma Membrane Transport Proteins Cell Line Tumor Virus latency Glutamate aspartate transporter medicine Immunology and Allergy Humans Tropism Cells Cultured Glycoproteins Pharmacology biology Brain Neoplasms Reverse Transcriptase Polymerase Chain Reaction Viral Core Proteins Glutamate receptor virus diseases Transporter biology.organism_classification medicine.disease Cell biology Virus Latency Excitatory Amino Acid Transporter 1 medicine.anatomical_structure Excitatory Amino Acid Transporter 2 Cell culture Astrocytes biology.protein Human herpesvirus 6 |
| Zdroj: | Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 3(2) |
| ISSN: | 1557-1904 |
| Popis: | Human herpesvirus 6 (HHV-6) infects and establishes latency in the central nervous system (CNS). Reactivation of latent HHV-6 has been associated with neurologic diseases including epilepsy and multiple sclerosis (MS). In vivo, HHV-6 has been localized to astrocytes and can infect human astrocytes in vitro, suggesting that this virus may have a tropism for glial cells and may affect glial cell function. An essential role of astrocytes in the CNS is active maintenance of the excitatory neurotransmitter glutamate. Dysregulation of glutamate has been implicated as a potential mechanism of disease in both epilepsy and MS. Both disorders have demonstrated elevated glutamate in CSF and may be associated with dysregulation of glutamate signaling, uptake, and metabolism. This study demonstrates dysregulation of glutamate uptake in human astrocytes infected with both variants of HHV-6, A and B, with differential effects of HHV-6 in acute and persistently infected cells. Whereas astrocytes acutely infected with HHV-6 demonstrated increased glutamate uptake, cells persistently infected with HHV-6A and HHV-6B demonstrated impaired glutamate uptake. Functional dysregulation of glutamate uptake was associated with early increases in mRNA and protein expression of the glial glutamate transporter EAAT-2 followed by a sustained decrease in mRNA expression in astrocytes infected with both HHV-6A and HHV-6B. Dysregulated glutamate uptake and transporter expression suggests a mechanism for dysregulation of glutamate levels in vivo and a potential mechanism for virus-associated neurologic disease. |
| Databáze: | OpenAIRE |
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