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Introduction: Chikungunya virus (CHIKV) infection is associated with acute clinical manifestations and chronic joint inflammation. CHIKV has emerged as a significant causative agent of central nervous system (CNS) complications, including encephalitis and related sequelae. Microglial cells, crucial for immune responses and tissue repair in the CNS, play a vital role in the host response to viral infections, with their activation potentially leading to either protection or pathology. In this study, the infection biology of CHIKV in the C20 human microglial cell line was investigated. Methods: The permissiveness of C20 cells to CHIKV infection was assessed, and viral replication kinetics were compared to Vero E6 cells. Cytopathic effects of CHIKV infection on C20 cells were examined, along with ultrastructural changes using transmission electron microscopy. Additionally, apoptosis induction, mitochondrial membrane potential, and alterations in cell surface marker expression were evaluated by flow cytometry. Results: CHIKV infection demonstrated permissiveness in C20 cells, similar to Vero cells, resulting in robust viral replication and cytopathic effects. Ultrastructural analysis revealed viral replication, mature virion formation, and distinctive cytoplasmic and nuclear changes in infected C20 cells. CHIKV infection induced significant apoptosis in C20 cells, accompanied by mitochondrial membrane depolarization and altered expression of cell surface markers such as CD11c, CD14, and HLA-DR. Notably, decreased CD14 expression was observed in CHIKV-infected C20 cells. Discussion: The study findings suggest that CHIKV infection induces apoptosis in C20 microglial cells via the mitochondrial pathway, with significant alterations in cell surface marker expression, particularly CD14 that is linked with apoptosis induction. These observations provide valuable insights into the role of human microglial cells in the host response to CHIKV infection and contribute to the knowledge on the neuropathogenesis of this virus. [ABSTRACT FROM AUTHOR]

Radiotherapy is an important treatment modality in the management of cancer. Nearly 60% of patients receive radiation - alone or in combination with chemotherapy. However, there are problems of tumour radio-resistance to treatment. For example, about 20% of the most aggressive gliomas do not respond to radio-chemotherapy. The survivors suffer from radio-necrosis, progressive loss of neurological functions (loss of cognitive integrity, speech and motor function, and intellectual abilities) as well as significant behavioral changes. Several approaches for reducing radio-toxicity in cancer therapy have been under active investigation. These include combination of protectors or sensitizers with radiotherapy. However, there have been limitations of selectivity of action as well as efficacy in several studies. Therefore, it is important to carry out further preclinical studies, to develop more effective treatment for these tumors. In our earlier studies, 2-deoxy-D-Glucose (2-DG), an inhibitor of glycolytic energy metabolism, was observed to differentially inhibit growth and repair of radiation damage in tumor cells; and increased tumor regression in experimental models. It did not lead to additional toxicities as radiosensitizer in clinical trials. In the present studies, effects of combining 2-DG with Temozolomide (TMZ) on different malignant glioma cell lines were studied. Exponentially growing cells were exposed to drug± radiation treatments, under clinically relevant experimental conditions. Drugs were removed 4 hours later and cultures were processed further for different assays of damage. Effects on proliferation response, viability, total cellular damage (TCD), cell cycle perturbations, biochemical and ultra-structural alterations were studied. Combination of 2-DG with TMZ resulted in biochemical and ultra-structural alterations and cell cycle perturbations. Combination of drugs with radiation significantly inhibited proliferation response and increased total cellular damage. Our studies suggest that 2-DG could significantly enhance the efficacy of TMZ-Radiation therapy and decrease the cumulative radiation dose required for treatment; reducing thereby its toxic side effects. [ABSTRACT FROM AUTHOR]