Biology subjects

Mok, B. W. Y.

Publications and source records attributed to Mok, B. W. Y..

3 recordsLinked to original sources

bioRxiv2025

SARS-CoV-2 Infects Peripheral Sensory Neurons and Promotes Axonal Degeneration via TRPV1 Activation

Common neurological symptoms of COVID-19, such as anosmia, headaches, and cognitive dysfunction, depend on interactions between the peripheral and central nervous systems. However, the molecular mechanisms by which SARS-CoV-2 affects the peripheral nervous system remain poorly understood, with ongoing debate about whether sensory neurons can be directly infected by the virus. In this study, human iPSC-derived sensory neurons were exposed to the SARS-CoV-2 BA.5 variant, a mutant virus, or viral S1 proteins. Under control conditions, sensory neurons exhibited low expression of ACE2. However, exposure to BA.5 or S1 proteins significantly upregulated ACE2 expression in peripherin-positive sensory neurons. Virological analysis confirmed that SARS-CoV-2 directly infects TRPV1-expressing sensory neurons, including olfactory neurons. Moreover, exposure to the live virus or S1 proteins induced TRPV1 upregulation and translocation from the nucleus to the cytosol, resulting in axonal destruction. Single-nucleus transcriptomic analysis revealed that viral exposure enhanced cAMP signaling, virus receptor and transmembrane transporter activities, and inflammatory regulation of TRP channels, which collectively contributed to synaptic and axonal damage. Importantly, treatment with a TRPV1 antagonist demonstrated neuroprotective effects. These findings underscore the need for further research into the interaction between SARS-CoV-2 and TRPV1, as well as its downstream signaling pathways, to develop therapeutic strategies for preventing sensory neuron loss during viral infections. HighlightsO_LIiPSC technology was employed to generate peripheral sensory neurons from human induced pluripotent stem cells (iPSCs), providing a valuable platform for studying the impact of SARS-CoV-2 on peripheral sensory neurons. C_LIO_LIOur findings demonstrated that the SARS-CoV-2 Omicron BA.5 variant exerted both direct and indirect effects on peripheral sensory neurons. Virus exposure upregulated the angiotensin-converting enzyme 2 (ACE2) receptor in peripherin-positive neurons. Additionally, exposure to the virus or its S1 spike protein increased transient receptor potential vanilloid 1 (TRPV1) expression and trafficking, leading to axonal degeneration. C_LIO_LISingle-nucleus RNA sequencing revealed that BA.5 exposure enhanced cAMP signaling pathway, virus receptor and transmembrane transporter activities, and inflammatory regulation of TRP channels that led to the significantly damage on synapses and axon guidance. C_LIO_LIThe TRPV1 antagonist capsazepine inhibited TRPV1 activation and mitigated axonal damage, offering neuroprotective effects for sensory neurons exposed to SARS-CoV-2. C_LI

cell biology↗

bioRxiv2022

The SARS-CoV-2 Omicron (B.1.1.529) variant exhibits altered pathogenicity, transmissibility, and fitness in the golden Syrian hamster model

The newly emerging SARS-CoV-2 Omicron (B.1.1.529) variant first identified in South Africa in November 2021 is characterized by an unusual number of amino acid mutations in its spike that renders existing vaccines and therapeutic monoclonal antibodies dramatically less effective. The in vivo pathogenicity, transmissibility, and fitness of this new Variant of Concerns are unknown. We investigated these virological attributes of the Omicron variant in comparison with those of the currently dominant Delta (B.1.617.2) variant in the golden Syrian hamster COVID-19 model. Omicron-infected hamsters developed significantly less body weight losses, clinical scores, respiratory tract viral burdens, cytokine/chemokine dysregulation, and tissue damages than Delta-infected hamsters. The Omicron and Delta variant were both highly transmissible (100% vs 100%) via contact transmission. Importantly, the Omicron variant consistently demonstrated about 10-20% higher transmissibility than the already-highly transmissible Delta variant in repeated non-contact transmission studies (overall: 30/36 vs 24/36, 83.3% vs 66.7%). The Delta variant displayed higher fitness advantage than the Omicron variant without selection pressure in both in vitro and in vivo competition models. However, this scenario drastically changed once immune selection pressure with neutralizing antibodies active against the Delta variant but poorly active against the Omicron variant were introduced, with the Omicron variant significantly outcompeting the Delta variant. Taken together, our findings demonstrated that while the Omicron variant is less pathogenic than the Delta variant, it is highly transmissible and can outcompete the Delta variant under immune selection pressure. Next-generation vaccines and antivirals effective against this new VOC are urgently needed. One Sentence SummaryThe novel SARS-CoV-2 Omicron variant, though less pathogenic, is highly transmissible and outcompetes the Delta variant under immune selection pressure in the golden Syrian hamster COVID-19 model.

microbiology↗

bioRxiv2020

SARS-CoV-2 spike D614G variant exhibits highly efficient replication and transmission in hamsters

SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster infection model to compare the replication ability and pathogenicity of five SARS-CoV-2 strains isolated from early cases originating in Wuhan, China, in February, and infected individuals returning from Europe and elsewhere in March 2020. The HK-13 and HK-95 isolates showed distinct pathogenicity in hamsters, with higher virus titers and more severe pathological changes in the lungs observed compared to other isolates. HK-95 contains a D614G substitution in the spike protein and demonstrated higher viral gene expression and transmission efficiency in hamsters. Intra-host diversity analysis revealed that further quasi species were generated during hamster infections, indicating that strain-specific adaptive mutants with advantages in replication and transmission will continue to arise and dominate subsequent waves of SARS-CoV-2 dissemination.

microbiology↗