SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion
cell biology immunology/immunity virology
Authors: X. Wang et al.
Link to paper: https://www.nature.com/articles/s41423-020-0424-9
Journal/ Pre-Print: Cellular and Molecular Immunology
Key Words: SARS-CoV2, T cells, infectivity
1. SARS-Cov2 can infect human T lymphocyte cell lines through Spike protein mediated membrane fusion
2. The viral fusion inhibiting EK1- peptide reduces SARS-Cov2 infectivity in T cell lines in very high concentration in vitro.
3. The low mRNA expression of hACE2 (viral entry receptor) in T cells suggests that another receptor might mediate the virus entry in T cells.
The authors assessed SARS-Cov2 infectivity of T cells that might explain lymphocytopenia found in some COVID-19 patients. Albeit a very low hACE2 mRNA expression their SARS-CoV-2 pseudovirus was able to enter (but not replicate) in human T lymphocyte cell line (MT-02 and A3.01) in a manner sensitive to a high concentration of Spike-protein fusion inhibitor EK1-peptide.
IMPACT FOR SARS-COV2/COVID19 RESEARCH EFFORTS
Understand the virology and/or cell biology of SARS-CoV2/COVID19 that might explain lymphocytopenia observed in some VOCID-19 patients.
· In vitro study
STRENGTHS AND LIMITATIONS OF THE PAPER
Novelty: suggest an explanation for one clinical symptom (lymphocytopenia)
Standing in the field: first paper to show that SARS-CoV-2 Spike fusion enables viral entry into human T cell lines.
Appropriate statistics: unpaired t-test performed in some graphs but no information about replicates reduce considerably the robustness!
Viral model used: pseudoviruses – SARS-CoV and SARS-CoV2
Translatability: Need to perform similar study on primary T cells (from healthy and patient donors) before evoking therapeutic interventions.
- in vitro, on cell lines and not primary human cells
- Did not measure ACE2 protein expression on T cell lines, and did not include a negative control sample for ACE2 mRNA
- Did not provide negative or toxicity controls for EK1 peptide effect
- Do not provide information about the number of replicates
- Inconsistency between 2 figures (1c and 1d – infection ability on MT-2 2000RLU then 8000)
- Very subtle shift on the MT2 infection FACS plot (Fig. 1f), no isotype or other control for non-specific labeling, would have been better to show the MFI?
- No quantification of syncytium formation
- No information on T cell death upon infection that would explain lymphocytopenia