Human iPS cell-derived sensory neurons can be infected by SARS-CoV-2

Anthony Flamier, Punam Bisht, Alexsia Richards, Danielle L. Tomasello, Rudolf Jaenisch

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

COVID-19 has impacted billions of people since 2019 and unfolded a major healthcare crisis. With an increasing number of deaths and the emergence of more transmissible variants, it is crucial to better understand the biology of the disease-causing virus, the SARS-CoV-2. Peripheral neuropathies appeared as a specific COVID-19 symptom occurring at later stages of the disease. In order to understand the impact of SARS-CoV-2 on the peripheral nervous system, we generated human sensory neurons from induced pluripotent stem cells that we infected with the SARS-CoV-2 strain WA1/2020 and the variants delta and omicron. Using single-cell RNA sequencing, we found that human sensory neurons can be infected by SARS-CoV-2 but are unable to produce infectious viruses. Our data indicate that sensory neurons can be infected by the original WA1/2020 strain of SARS-CoV-2 as well as the delta and omicron variants, yet infectability differs between the original strain and the variants.

Original languageEnglish
Article number107690
JournaliScience
Volume26
Issue number9
DOIs
StatePublished - 15 Sep 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Funding

We thank members in the laboratories of Rudolf Jaenisch and Richard Young and other colleagues from Whitehead Institute and MIT for helpful discussions and resources. We thank Wendy Salmon from the Whitehead W.M. Keck Microscopy Facility and Whitehead Genome Core Facility. This work was supported by grants from the NIH (U19AI131135 and R01MH104610). This work was performed in part in the Ragone Institute BSL3 core, which is supported by the NIH-funded Harvard University Center for AIDS Research (P30 AI060354). Project design by A.F.; execution of experiments by A.F. P.B. A.R. and D.T.; data analysis by A.F. A.R. and D.T.; manuscript preparation by A.F. P.B. A.R. D.T. and R.J. R.J. is an advisor/co-founder of Fate Therapeutics, Fulcrum Therapeutics, Omega Therapeutics, and Paratus Therapeutics. A.F. is a co-founder and shareholder of StemAxon. All other authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. We thank members in the laboratories of Rudolf Jaenisch and Richard Young and other colleagues from Whitehead Institute and MIT for helpful discussions and resources. We thank Wendy Salmon from the Whitehead W.M. Keck Microscopy Facility and Whitehead Genome Core Facility. This work was supported by grants from the NIH ( U19AI131135 and R01MH104610 ). This work was performed in part in the Ragone Institute BSL3 core, which is supported by the NIH -funded Harvard University Center for AIDS Research ( P30 AI060354 ).

FundersFunder number
Fate Therapeutics
Fulcrum Therapeutics
Omega Therapeutics
Paratus Therapeutics
National Institutes of HealthU19AI131135, R01MH104610
Massachusetts Institute of Technology
Harvard University Center for AIDS ResearchP30 AI060354
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology

    Keywords

    • Cellular neuroscience
    • Neuroscience
    • Virology

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