Publications by authors named "Ahmad S Rashidi"
Usutu (USUV), West Nile (WNV), and Zika virus (ZIKV) are neurotropic arthropod-borne viruses (arboviruses) that cause severe neurological disease in humans. However, USUV-associated neurological disease is rare, suggesting a block in entry to or infection of the brain. We determined the replication, cell tropism and neurovirulence of these arboviruses in human brain tissue using a well-characterized human fetal organotypic brain slice culture model.
View Article and Find Full Text PDFBackground: Herpes simplex virus (HSV) encephalitis (HSE) is a serious and potentially life-threatening disease, affecting both adults and newborns. Progress in understanding the virus and host factors involved in neonatal HSE has been hampered by the limitations of current brain models that do not fully recapitulate the tissue structure and cell composition of the developing human brain in health and disease. Here, we developed a human fetal organotypic brain slice culture (hfOBSC) model and determined its value in mimicking the HSE neuropathology in vitro.
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- - Neurotropic viruses like HSV-1 and HSV-2 can infect neurons, leading to cell death and potentially severe health issues if not managed.
- - The study shows that HSV-2 infection triggers a specific cell death pathway in neuron-like and brain cells through gasdermin E (GSDME), following endoplasmic reticulum (ER) stress caused by IRE1α activation.
- - This process involves the activation of caspases and leads to the release of inflammatory signals (alarmins) from dying neurons, which in turn stimulates an immune response in microglia.
Spread of herpes simplex virus 1 (HSV1) from the periphery to the central nervous system (CNS) can lead to extensive infection and pathological inflammation in the brain, causing herpes simplex encephalitis (HSE). It has been shown that microglia, the CNS-resident macrophages, are involved in early sensing of HSV1 and induction of antiviral responses. In addition, infiltration of peripheral immune cells may contribute to the control of viral infection.
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- The type I interferon (IFN-I) system is crucial for protecting the brain from viral infections, but both too little and too much of it can lead to issues, such as susceptibility to herpes simplex encephalitis (HSE).
- Research using mouse models and human cases revealed that immune cells in the infected brain, particularly microglia, undergo apoptosis (cell death) in response to the virus through a mechanism that involves the cGAS/STING pathway, but this process does not rely on IFN-I levels.
- By inhibiting caspase activity, researchers found that it prevented cell death in microglia, enhanced IFN-I responses, reduced viral load, and improved infection outcomes in both organotypic