SARS-CoV-2 Variants from Long-Term, Persistently Infected Immunocompromised Patients Have Altered Syncytia Formation, Temperature-Dependent Replication, and Serum Neutralizing Antibody Escape
Abstract
:1. Introduction
2. Methods
2.1. Institutional Review Board Approvals
2.2. Cell Culture
2.3. Virus Plaque Picking, Seed Stock, and Working Stock Generation
2.4. Sequencing of Plaque-Picked SARS-CoV-2 Isolates
2.5. Tissue Culture Infectious Dose (TCID50) Assay
2.6. Vero/TMPRSS2 Infections
2.7. Human Nasal Epithelial Cell (hNEC) Infections
2.8. Plaque Reduction Neutralization Test (PRNT)
2.9. Spike Plasmid Preparation
2.10. Flow Cytometry for Surface Spike
2.10.1. mCherry Lentivirus Production
2.10.2. Lentivirus Transduction and Clonal Cell Selection for Stable Expression of mCherry in Vero/TMPRSS2 Cells
2.11. Syncytia Assay
2.12. Statistical Analyses
3. Results
3.1. Plaque-Picked Virus Stocks Have Multiple Mutations Compared to the Initial Infecting Virus That Align with Global Variants of Concern
3.2. Patient 2 Virus Isolates Have Distinct Plaque Sizes and Temperature-Dependent Replication Differences on Vero/TMPRSS2 Cells and hNECs
3.3. Patient 2 Virus Isolates Do Not Show Escape from Neutralization with Convalescent Plasma
3.4. Patient 2 Virus Isolates Do Not Show Altered Syncytia Formation over the Course of Infection
3.5. Patient 3 Virus Isolates Have Different Plaque Sizes but No Distinct Replication Differences on hNECs
3.6. Patient 3 Day 139 Virus Has Increased Escape from Neutralizing Convalescent Plasma Antibodies
3.7. Day 139 Spike Has Increased Syncytia Formation versus Day 0 Spike
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CM | Complete media |
CPE | Cytopathic effect |
hNEC | Human nasal epithelial cell |
ICPs | Immunocompromised patients |
IM | Infection media |
NTD | N-terminal Domain |
PRNT | Plaque Reduction Neutralization Test |
RBD | Receptor Binding Domain |
SNPs | Single nucleotide polymorphisms |
References
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Wouters, C.; Sachithanandham, J.; Akin, E.; Pieterse, L.; Fall, A.; Truong, T.T.; Bard, J.D.; Yee, R.; Sullivan, D.J.; Mostafa, H.H.; et al. SARS-CoV-2 Variants from Long-Term, Persistently Infected Immunocompromised Patients Have Altered Syncytia Formation, Temperature-Dependent Replication, and Serum Neutralizing Antibody Escape. Viruses 2024, 16, 1436. https://doi.org/10.3390/v16091436
Wouters C, Sachithanandham J, Akin E, Pieterse L, Fall A, Truong TT, Bard JD, Yee R, Sullivan DJ, Mostafa HH, et al. SARS-CoV-2 Variants from Long-Term, Persistently Infected Immunocompromised Patients Have Altered Syncytia Formation, Temperature-Dependent Replication, and Serum Neutralizing Antibody Escape. Viruses. 2024; 16(9):1436. https://doi.org/10.3390/v16091436
Chicago/Turabian StyleWouters, Camille, Jaiprasath Sachithanandham, Elgin Akin, Lisa Pieterse, Amary Fall, Thao T. Truong, Jennifer Dien Bard, Rebecca Yee, David J. Sullivan, Heba H. Mostafa, and et al. 2024. "SARS-CoV-2 Variants from Long-Term, Persistently Infected Immunocompromised Patients Have Altered Syncytia Formation, Temperature-Dependent Replication, and Serum Neutralizing Antibody Escape" Viruses 16, no. 9: 1436. https://doi.org/10.3390/v16091436