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Dissertation Defense: From entry to dysfunction: SARS-CoV-2 neuropathogenesis in peripheral sensory and autonomic neurons and Its implications

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Mary Frazier

Dissertation Defense: From entry to dysfunction: SARS-CoV-2 neuropathogenesis in peripheral sensory and autonomic neurons and its implications

Jonathan Joyce

Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Department of Population Health Sciences
May 1, 2025, at 12 p.m.

Integrated Life Sciences Building, Room 1040

Watch via Zoom

More About the Candidate and Project

Education

Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate

Virginia Tech, M.P.H., Infectious Diseases

University of Floriday, M.S., Microbiology & Cell Science

Radford University, B.S., Biology

Training

Graduate Research Assistant, Department of Population Health Sciences

Mentor

Andrea Bertke, Ph.D., Associate Professor, Infectious Diseases in Public Health

Committee Members

  • Joyce, JD., Moore, GA., Green, JC., Irwin, MD., Thompson, CK., Bertke, AS. (2025). SARS-CoV-2 Omicron XBB1.5 Shows Altered Replication In Neurons Versus Ancestral WA1/2020. Viruses (in press)
  • Joyce, JD., Moore, GA., Thompson, CK., Bertke, AS. (2025). Guinea pigs are not a suitable model to study neurological impacts of ancestral SARS-CoV-2 infection. Viruses (in press)
  • Joyce, JD., Moore, GA., Goswami, P., Harrell, TL., Taylor, TM., Hawks, SA., Green, JC., Jia, M., Irwin, M., Leslie, EH., Duggal, NK., Thompson, CK., Bertke, AS. (2024). SARS-CoV-2 Rapidly Infects Peripheral Sensory and Autonomic Neurons, Contributing to Central Nervous System Neuroinvasion before Viremia. Int. J. Mol. Sci, 25(15). https://doi.org/10.3390/ijms25158245
  • Jia, M., Joyce, JD., Bertke, AS. (2022). SARS-COV-2 survival in common non-alcoholic and alcoholic beverages. Foods, 11(6). https://doi.org/10.3390/foods11060802
  • Dhakal, J., Jia, M., Joyce, JD., Moore, GM., Ovissipour, R., Bertke, AS. (2021). Survival of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Herpes Simplex Virus 1 (HSV-1) on Foods Stored at Refrigerated Temperature. Foods, 10(5). https://doi.org/10.3390/foods10051005
  • Joyce, JD., Patel, AK., Murphy, B., Carr, DJ., Gershburg, E., Bertke, AS. (2021). Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs. Vaccines, 9(3). https://doi.org/10.3390/vaccines9030258
  • Best Oral Presentation - VT School of Neuroscience Summer Research Retreat 2023
  • Travel grant - American Society for Virology 2023
  • Best Oral Presentation – American Society for Microbiology VA Branch 2022
  • Travel grant – American Society for Microbiology VA Branch 2022
  • Best Poster Presentation - VT Alliance for Neurodevelopment 2022
  • Trainee Professional Development Award - Society for Neuroscience 2021
  • 4th Annual Meeting of the American Society for Virology – July 2025
    oComparative Growth Kinetics of La Crosse Virus 78V and NC97 Across Key Cell Types Affected in Adult and Childhood Infections (Accepted Oral Presentation)
  • 43rd Annual Meeting of the American Society for Virology – June 2024
    oSARS-CoV-2 Omicron XBB1.5 Shows Altered Replication In Neurons Versus Ancestral WA1/2020, Facilitated By NRP-1 (Accepted as Oral Presentation)
  • VT Translational Biology, Medicine and Health Winter Research Symposium – Dec. 2023
    oSARS-CoV-2 Omicron XBB1.5 Shows Altered Replication In Neurons Versus Ancestral WA1/2020, Facilitated By NRP-1 (Poster)
  • VT Center for Emerging, Zoonotic, and Arthropod-borne Pathogens (CeZAP) Infectious Diseases Symposium – Oct. 2023
    oSARS-CoV-2 Omicron XBB1.5 Shows Altered Replication In Neurons Versus Ancestral WA1/2020, Facilitated By NRP-1 (Oral)
  • VT School of Neuroscience Summer Research Retreat – July 2023
    oSARS-CoV-2 infects peripheral and central neurons before viremia, facilitated by Neuropilin-1 (Oral)
  • 42nd Annual Meeting of the American Society for Virology – June 2023
    oSARS-CoV-2 Rapidly Infects the Peripheral and Central Nervous Systems of Golden Syrian Hamsters and Produces Sensory Impairment (Poster)
  • VT Center for Emerging, Zoonotic, and Arthropod-borne Pathogens (CeZAP) Distinguished Speaker Seminar Series in Infectious Diseases – Jan. 2023
    oSARS-CoV-2 Rapidly Infects the Peripheral and Central Nervous Systems via Neuronal Entry Facilitated by Neuropilin-1 Before Detectable Viremia (Oral)
  • VT Translational Biology, Medicine and Health Winter Research Symposium – Jan. 2023
    oSARS-CoV-2 Rapidly Infects the Peripheral and Central Nervous Systems of Mice and Hamsters via Neuronal Entry Facilitated by Neuropilin-1 Before Detectable Viremia (Poster)
  • American Society for Microbiology VA Branch Meeting – Nov. 2022
    oSARS-CoV-2 Rapidly Infects the Peripheral and Central Nervous Systems via Neuronal Entry Facilitated by Neuropilin-1 Before Detectable Viremia (Oral)
  • VT Center for Emerging, Zoonotic, and Arthropod-borne Pathogens (CeZAP) Infectious Diseases Symposium – Oct. 2022
    oSARS-CoV-2 Rapidly Infects the Peripheral and Central Nervous Systems of Mice and Hamsters via Neuronal Entry Facilitated by Neuropilin-1 Before Detectable Viremia (Poster)
  • VT Alliance for Neurodevelopment – Aug. 2022
    oSARS-CoV-2 Rapidly Infects the Peripheral and Central Nervous Systems of Mice via Neuronal Entry Facilitated by Neuropilin-1 Before Detectable Viremia (Poster)
  • Let’s Meet the Virologist Podcast – June 2022
    oLMtV Episode 71: Let’s Meet the Virologist Jonathan Joyce
  • VT Virology group meeting – June 2022
    oSARS-CoV-2 in the Peripheral and Central Nervous System (Oral)
  • 41st Annual Meeting of the American Society for Virology – July 2022
    oSARS-CoV-2 Productively Infects the Peripheral Nervous System and Specific Brain Regions in Mice (Oral)
  • Integrated Life Science Building Spring 2022 Seminar– April 2022
    oSARS-CoV-2 in the Peripheral and Central Nervous System (Oral)
  • Fralin Biomedical Research Institute 9th Annual Brain School– Mar. 2022
    oSARS-CoV-2: On Your Last Nerve? (Poster)
  • Society for Neuroscience, Neuroscience 2021 – Nov. 2021
    oSensory and Autonomic Ganglia of the Peripheral Nervous System are Permissive to Infection with SARS-CoV-2 and May Provide an Avenue of Neural Invasion in K18-hACE2 mice (Poster and Oral)
  • 45th Annual International Herpesvirus Workshop – Aug. 2021
    oAssessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs (Poster)

Volunteer Service:


  • EMT-Intermediate, Bassett Volunteer Rescue Squad
  • EMT-Education Coordinator, Bassett Volunteer Rescue Squad
  • Infection Control Officer, Bassett Volunteer Rescue Squad

Outreach/Invited Talks:

  • Virginia Tech, College of Science, Pathways Course, Sept. 2022, “Neurovirology in Action: Exploring the Intersection of Neuroscience and Virology During the SARS-CoV-2 Pandemic” 
  • Virginia Tech, Department of Public Health Science, Emerging Infectious Diseases Course, Nov. 2022, “Bridging the Gap: Delivering Effective Infectious Disease Presentations for Lay Audiences”
  • Henry County Department of Public Safety, Continuing Education Event, Dec. 2022, “EMS in the Time of Emerging & Re-emerging Infectious Diseases”
  • Henry County Department of Public Safety, Continuing Education Event, Feb. 2024, “Sexually Transmitted Infections: Let’s Talk About Sex”
  • Virginia Tech, Corporate Research Center, Game Changers Week, Sept. 2024, “Breaking New Ground: Unraveling Neurotropic Virus Infections in the Peripheral Nervous System”
  • Bassett Volunteer Rescue Squad, Continuing Education Event, Oct. 2024, “Infectious Disease Update”
  • Virginia Tech, Department of Biological Sciences, Careers in Microbiology Course, Oct. 2024, “Bridging Biology and Public Health: How an MPH Shaped My Career as a Biologist

About this Dissertation

Neurological symptoms affecting the central nervous system (CNS) and peripheral nervous system (PNS) have become increasingly recognized as significant complications, both acute and long-term, associated with SARS-CoV-2 infection. While most research has focused on the CNS, minimal attention has been given to the susceptibility of the PNS to SARS-CoV-2 infection and its role in CNS invasion. We show that both sensory and autonomic neurons in the PNS are highly susceptible to SARS-CoV-2 infection, with replication occurring in neurons, satellite glial cells, and functionally connected CNS tissues. In particular, we demonstrate that SARS-CoV-2 invades the PNS before viremia and establishes a productive infection within peripheral neurons. Our studies in K18-hACE2 mice, wild-type mice, and golden Syrian hamsters, as well as primary neuronal cultures, show the presence of viral RNA, proteins, and infectious virus in PNS neurons and supporting cells as early as 18 hours post infection. Importantly, we identify neuropilin-1 (NRP-1) as an entry factor facilitating viral entry into these neurons. Using a contemporary SARS-CoV-2 variant, we show that XBB1.5 establishes a productive infection with distinct replication kinetics that are more attenuated when compared to ancestral WA1/2020. These findings show that SARS-CoV-2 replication dynamics in the PNS may differ across variants, potentially influencing severity and persistence of neurological symptoms. In addition to this work, we also evaluated the susceptibility of guinea pigs to intranasal infection with SARS-CoV-2 as a model for studying PNS involvement in COVID-19. Despite their utility in studying SARS-CoV-1, guinea pigs were resistant to infection with ancestral SARS-CoV-2 WA1/2020, highlighting limitations in their use for investigating neurological sequelae associated with SARS-CoV-2 infection and calling into question their continued use for evaluation of SARS-CoV-2 therapeutics. Our findings provide compelling evidence that SARS-CoV-2 directly infects the PNS and establishes a productive infection in peripheral neurons, leading to sensory impairments and contributing to the broader spectrum of neurological symptoms observed in COVID-19, including trigeminal neuralgia, Horner syndrome, and neuralgia. These insights should inform future therapeutic strategies to mitigate the neurological sequelae of infection with SARS-CoV-2 as it transitions from a pandemic virus to and endemic virus.