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Published on: February 19, 2019
Modeling extrahepatic hepatitis E virus infection in induced human primary neurons
Michelle Jagst1,2, André Gömer1, Sanja Augustyniak3
1Department for Molecular and Medical Virology, Institute for Hygiene and Microbiology, Ruhr University Bochum, Bochum 44801, Germany.
Hepatitis E virus (HEV) can infect neurons, causing neurological issues. This study reveals HEV disrupts neurite growth and evades immune responses in a novel human neuron model, offering insights into viral pathogenesis.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Hepatitis E virus (HEV) causes significant global mortality from acute viral hepatitis.
- HEV is increasingly linked to neurological disorders, but its pathogenesis remains unclear.
- Extrahepatic manifestations of HEV, particularly neurological impacts, require further investigation.
Purpose of the Study:
- To investigate Hepatitis E virus (HEV) extrahepatic manifestations using a human neuronal model.
- To elucidate the pathogenesis of HEV-associated neurological disorders.
- To establish a human-induced primary neuron (iPN) system for studying HEV infection.
Main Methods:
- Reprogramming human renal epithelial cells to induced pluripotent stem cells, then differentiating into iPNs.
- Infecting iPNs with HEV and analyzing viral dynamics and host responses.
- Utilizing transcriptional profiling and 3D reconstruction to visualize viral protein and neurite changes.
Main Results:
- HEV successfully infected iPNs, particularly in neurite-bearing cells.
- HEV infection led to reduced neurite length in a dose-dependent manner.
- Neurons exhibited a weak innate immune response to HEV, with limited interferon signaling.
Conclusions:
- The developed iPN model is effective for studying HEV extrahepatic manifestations.
- HEV infection in neurons may involve impaired neurite growth and host-pathogen interactions.
- The study suggests a potential pathogenic mechanism for HEV-induced neurological diseases.
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