1. Cytoprotective effects of lithium on endothelial integrity and immune profiles induced by rift valley fever virus on huvec and raw 264.7 cells
- Author
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Makola, Raymond Tshepiso, Matsebatlela, T. M., Paweska, J. T., Jan Van Vuren, Petrus, Makola, Raymond Tshepiso, Matsebatlela, T. M., Paweska, J. T., and Jan Van Vuren, Petrus
- Abstract
Introduction: Rift Valley fever virus (RVFV) is an arthropod-born RNA zoonotic virus causing Rift Valley fever (RVF) disease. RVFV is prevalent across sub-Saharan Africa and the Arabian Peninsula with no existing effective and approved antiviral remedies for humans or animals. RVFV has developed mechanisms to hide from immune recognition and induce anti-apoptosis processes to keep the infected host cells viable in an attempt to advance their viral progeny. RVFV is a single-stranded enveloped RNA genome virus composed of 3 segments; the L, M and S segments. The S segment is known to encode a non-structural protein (NSs) identified to be the main virulence factor promoting viral replication through immune suppression. RVFV elicits a set of diverse symptoms ranging from a febrile illness to more severe symptoms that usually culminate in life-threatening haemorrhagic fever with high fatality rates. Thus, this study was designed to investigate the efficacy of lithium as a potential drug for reduction of RVFV load and amelioration of imbalanced and dysregulated inflammatory responses observed in Huvec and Raw 264.7 macrophages infected with this virus. Methods and results: The MTT and Cyquant viability assays were used to demonstrate that lithium exerts no cytotoxic effects on non-infected Raw 264.7 macrophage cells but rather promotes cell growth and proliferation. Conversely, lithium was shown to significantly induce cell death in RVFV-infected Raw 264.7 macrophages. The Annexin-V/PI apoptosis assay was employed to demonstrate that RVFV induces apoptosis as a mode of cell death on Raw 264.7 cells. RVFV-induced apoptosis was accompanied by antagonistic Bax/Bcl-2 protein expression ratios. RVFV-infected cells treated with lithium resulted in higher levels of apoptosis signals compared to untreated RVFV-infected cells. Analysis of apoptosis stages using the real-time cell analyser (RTCA) also revealed that lithium induced early forms of apoptosis in RVFV-infected cells. In, Poliomyelitis Research foundation and National Research Foundation
- Published
- 2022