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Conference Paper: The Impact of SARS-CoV-2 on iPSC-Derived Sensory Neurons

TitleThe Impact of SARS-CoV-2 on iPSC-Derived Sensory Neurons
Authors
Issue Date29-Sep-2024
Abstract

Introduction

Infection with SARS-CoV-2 may have  impact on multiple organs. Apart from targeting the respiratory system, SARS-CoV-2 virus may cause neurological symptoms such as anosmia and headache, etc. 59% of COVID-19 patients are estimated to show signs of neuropathy in the mid or long term. However, current reports are inconsistent in regard of    whether neural cells can be infected by SARS-CoV-2, with some studies suggest low susceptibility to the virus as neurons have low ACE2 expression, and neuropathies are a result of indirect mechanisms instead of direct infection, while  other research shows that neurons do express ACE2 and can be infected. Here, we aim to resolve this controversy by employing iPSC-derived sensory neurons to investigate the impact of SARS-CoV-2 on neural cells and elucidate the molecular mechanisms of virus-induced neuropathies..

Methods

iPSCs were differentiated into a heterogenous population of sensory neurons, and expression of  ACE2 and TMPRSS2 were assessed. Subsequently, the sensory neurons were exposed to SARS-CoV-2 viruses (BA5 variant), spike protein or influenza virus for 48 hours. Immunofluorescence analysis was performed to assess expression level and pattern of ACE2, TMPRSS2, and TRPV1 within the neuron population.

Results

Most iPSC-derived sensory neurons express ACE2 and TMPRSS2. Exposure to Omicron BA5 virus showed infection in some neurons and upregulated the overall expression of ACE2 and Transient Receptor Potential Vanilloid 1 (TRPV1). Additionally, viral exposure induced cell death in the sensory neurons. Increased blebbing and weakened neuronal network were observed in cells exposed to the virus. Administration of TRPV1 antagonist capsazepine had a protective effect on the neurons and reduced cell death.

Conclusions

Our research emphasizes the expression and activation of ACE2 and TMPRSS2 in sensory neurons upon exposure to viruses. The induction of cell death by SARS-CoV-2 through TRPV1 activation in these neurons could potentially reveal the molecular mechanisms underlying virus-induced neuropathies.


Persistent Identifierhttp://hdl.handle.net/10722/353586

 

DC FieldValueLanguage
dc.contributor.authorCo, Vanessa Anna-
dc.contributor.authorLiu, Siwen-
dc.contributor.authorMok, Bobo Wing Yee-
dc.contributor.authorChen, Honglin-
dc.contributor.authorHong, Yiling-
dc.date.accessioned2025-01-21T00:35:50Z-
dc.date.available2025-01-21T00:35:50Z-
dc.date.issued2024-09-29-
dc.identifier.urihttp://hdl.handle.net/10722/353586-
dc.description.abstract<p><strong>Introduction</strong></p><p>Infection with SARS-CoV-2 may have  impact on multiple organs. Apart from targeting the respiratory system, SARS-CoV-2 virus may cause neurological symptoms such as anosmia and headache, etc. 59% of COVID-19 patients are estimated to show signs of neuropathy in the mid or long term. However, current reports are inconsistent in regard of    whether neural cells can be infected by SARS-CoV-2, with some studies suggest low susceptibility to the virus as neurons have low ACE2 expression, and neuropathies are a result of indirect mechanisms instead of direct infection, while  other research shows that neurons do express ACE2 and can be infected. Here, we aim to resolve this controversy by employing iPSC-derived sensory neurons to investigate the impact of SARS-CoV-2 on neural cells and elucidate the molecular mechanisms of virus-induced neuropathies..</p><p><strong>Methods</strong></p><p>iPSCs were differentiated into a heterogenous population of sensory neurons, and expression of  ACE2 and TMPRSS2 were assessed. Subsequently, the sensory neurons were exposed to SARS-CoV-2 viruses (BA5 variant), spike protein or influenza virus for 48 hours. Immunofluorescence analysis was performed to assess expression level and pattern of ACE2, TMPRSS2, and TRPV1 within the neuron population.</p><p><strong>Results</strong></p><p>Most iPSC-derived sensory neurons express ACE2 and TMPRSS2. Exposure to Omicron BA5 virus showed infection in some neurons and upregulated the overall expression of ACE2 and Transient Receptor Potential Vanilloid 1 (TRPV1). Additionally, viral exposure induced cell death in the sensory neurons. Increased blebbing and weakened neuronal network were observed in cells exposed to the virus. Administration of TRPV1 antagonist capsazepine had a protective effect on the neurons and reduced cell death.</p><p><strong>Conclusions</strong></p><p>Our research emphasizes the expression and activation of ACE2 and TMPRSS2 in sensory neurons upon exposure to viruses. The induction of cell death by SARS-CoV-2 through TRPV1 activation in these neurons could potentially reveal the molecular mechanisms underlying virus-induced neuropathies.</p>-
dc.languageeng-
dc.relation.ispartofOptions XII for the Control of Influenza (29/09/2024-02/10/2024, Brisbane)-
dc.titleThe Impact of SARS-CoV-2 on iPSC-Derived Sensory Neurons-
dc.typeConference_Paper-

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