Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion

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

Research Highlights 

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.

Summary

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.

Study Type

· 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.

Main limitations:

- 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