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Thailand Medical News Team  Aug 20, 2023  8 months, 1 week, 7 hours, 37 minutes ago

BREAKING NEWS! Study Finds That Human iPS Cell-Derived Sensory Neurons Susceptible to SARS-CoV-2 Infection: Implications for COVID-19 Neuropathies

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BREAKING NEWS! Study Finds That Human iPS Cell-Derived Sensory Neurons Susceptible to SARS-CoV-2 Infection: Implications for COVID-19 Neuropathies
Thailand Medical News Team  Aug 20, 2023  8 months, 1 week, 7 hours, 37 minutes ago
COVID-19 News: Since its emergence in 2019, the COVID-19 pandemic has caused significant global health challenges, leading to an urgent need for understanding the intricate interactions between the SARS-CoV-2 virus and various human tissues. While the primary impact of the virus has been well-documented within the respiratory system, its effects on the nervous system have also been increasingly recognized. Studies and COVID-19 News reports have linked SARS-CoV-2 infection to various neurological symptoms, including anosmia (loss of smell), headaches, stroke, delirium, and brain inflammation, highlighting the virus's potential to affect the peripheral nervous system as well as the central nervous system.


                                                                                        Graphical Abstract
 
Peripheral Neuropathies and the Need for Further Investigation
Among these neurological symptoms, peripheral neuropathies, characterized by damage to the peripheral nerves, have emerged as notable manifestations of COVID-19. These neuropathies have been reported to occur at later stages of the disease and are estimated to impact approximately 59% of COVID-19 patients in the medium- to long-term. This phenomenon has raised questions about the mechanisms through which SARS-CoV-2 interacts with the peripheral nervous system and triggers neuropathies.
 
Exploring Sensory Neuron Susceptibility to SARS-CoV-2
To gain insights into the interaction between SARS-CoV-2 and the peripheral nervous system, researchers at the Whitehead Institute for Biomedical Research and the Department of Biology at the Massachusetts Institute of Technology conducted a study using human-induced pluripotent stem (iPS) cells. The researchers aimed to investigate whether sensory neurons derived from iPS cells could be infected by the SARS-CoV-2 virus and whether this infection could shed light on the underlying mechanisms of COVID-19-related neuropathies.
 
Infection and Variability
The study utilized the original WA1/2020 strain of SARS-CoV-2 as well as the delta and omicron variants to infect the iPS cell-derived sensory neurons. The researchers employed single-cell RNA sequencing (scRNAseq) to analyze the infection patterns and found that approximately 20% of the sensory neurons showed susceptibility to SARS-CoV-2 infection. Interestingly, the omicron variant exhibited the lowest infection rate among the strains tested. This observation highlights the potential differences in infectability between the original strain and its variants, suggesting a complex interplay between the virus and the host cells.
 
ong>Sensory Neurons as Infection Targets
Contrary to previous assumptions that neurons are not susceptible to SARS-CoV-2 due to the absence of ACE2 expression - the receptor through which the virus gains entry - the study's findings demonstrated that sensory neurons of the peripheral nervous system can indeed be infected by the SARS-CoV-2 virus. While olfactory sensory neurons and cortical neurons were believed to lack the necessary receptors for infection, recent evidence suggests that specific subtypes of sensory neurons express ACE2 and can be targeted by SARS-CoV-2. This includes the outer segment of photoreceptors and nociceptor sensory neurons found in the dorsal root ganglion of COVID-19 patients.
 
Mechanisms of Infection and Replication
Remarkably, despite the susceptibility of sensory neurons to infection, the study revealed that these cells do not actively replicate the virus to generate progeny virions, as indicated by plaque assays. This intriguing finding raises questions about the mechanisms underlying this non-productive infection.
 
One avenue of investigation is the role of tyrosine kinases, which are known to be involved in antiviral responses. The repression of these kinases in infected sensory neurons may contribute to the observed lack of viral packaging and release.
 
Additionally, the phase separation of nucleocapsid protein with viral RNA plays a crucial role in the production of virions. The downregulation of specific hnRNPs (FUS, hnRNPD, and hnRNPA2B1) in infected sensory neurons may impair this phase separation, further hindering virion assembly.
 
Implications for Neuropathies
The findings of this study shed light on the potential mechanisms underlying COVID-19-related neuropathies. Sensory neurons from the dorsal root ganglion, which project from the lungs to the spinal cord, could become infected due to the high viral load in the lungs of COVID-19 patients. The non-productive infection observed in these neurons might explain the peripheral neuropathies observed in COVID-19 patients, offering a new perspective on the pathogenesis of these symptoms.
 
Conclusion
As the world continues to grapple with the impact of the COVID-19 pandemic, research into the virus's interactions with various human tissues remains critical. The study conducted by the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology offers valuable insights into the susceptibility of sensory neurons to SARS-CoV-2 infection and the potential mechanisms behind non-productive infections. These findings pave the way for further investigations into the intricate relationships between the virus and the nervous system, ultimately contributing to a deeper understanding of COVID-19-related neuropathies and potential therapeutic interventions.
 
The study findings were published in the peer reviewed journal: iScience.
https://www.sciencedirect.com/science/article/pii/S2589004223017674
 
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