CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment
SARS-CoV-2 infection induces the generation of virus-specific CD4<sup>+</sup> and CD8<sup>+</sup> effector and memory T cells. However, the contribution of T cells in controlling SARS-CoV-2 during infection is not well understood. Following infection of C57BL/6 mice, SARS-CoV-2-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cells are recruited to the respiratory tract, and a vast proportion secrete the cytotoxic molecule granzyme B. Using depleting antibodies, we found that T cells within the lungs play a minimal role in viral control, and viral clearance occurs in the absence of both CD4<sup>+</sup> and CD8<sup>+</sup> T cells through 28 days postinfection. In the nasal compartment, depletion of both CD4<sup>+</sup> and CD8<sup>+</sup> T cells, but not individually, results in persistent, culturable virus replicating in the nasal epithelial layer through 28 days postinfection. Viral sequencing analysis revealed adapted mutations across the SARS-CoV-2 genome, including a large deletion in ORF6. Overall, our findings highlight the importance of T cells in controlling virus replication within the respiratory tract during SARS-CoV-2 infection.
Authors
- Meredith E. Davis-Gardner (ORCID: https://orcid.org/0000-0002-6133-3613)
- Eduardo Salinas (ORCID: https://orcid.org/0000-0002-4490-9289)
- Swathi Shrihari (ORCID: https://orcid.org/0000-0002-8188-6936)
- Arash Grakoui (ORCID: https://orcid.org/0000-0002-6002-7518)
- Mehul S. Suthar (ORCID: https://orcid.org/0000-0002-2686-8380)
- Amelia K. Pinto (ORCID: https://orcid.org/0000-0002-7147-3978)
- Robyn S. Klein (ORCID: https://orcid.org/0000-0003-0281-1352)
- Abigail Vanderheiden (ORCID: https://orcid.org/0000-0003-1321-4510)
- Shruti Sathish
- Stephanie Banakis
- Meenakshi Kar (ORCID: https://orcid.org/0000-0003-3332-811X)
- Jacob E. Kohlmeier (ORCID: https://orcid.org/0000-0002-7209-6641)
- Katharine Floyd (ORCID: https://orcid.org/0000-0002-0866-6961)
- Elizabeth J. Elrod (ORCID: https://orcid.org/0000-0003-1236-5309)
- Elizabeth Geerling (ORCID: https://orcid.org/0000-0002-5104-499X)
- E. Taylor Stone (ORCID: https://orcid.org/0000-0001-6742-1270)
- Elodie Ghedin (ORCID: https://orcid.org/0000-0002-1515-725X)
- Katherine Johnson (ORCID: https://orcid.org/0000-0002-9226-0672)
- Wei Wang (ORCID: https://orcid.org/0009-0004-6516-1363)
Institutions
- Western University (CA)
- National Institutes of Health (US)
- Emory University (US)
- Washington University in St. Louis (US)
- Children's Healthcare of Atlanta (US)
- Emory National Primate Research Center
- Saint Louis University (US)
Publication Details
- Journal
- Science Advances
- Published
- 2024-08-23
- DOI
- https://doi.org/10.1126/sciadv.adp2636
- Citations
- 17
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 6.61
Funders
- Emory University
- National Institutes of Health