ACE2-independent infection of T lymphocytes by SARS-CoV-2

Here’s a detailed summary of the study titled “ACE2-independent infection of T lymphocytes by SARS-CoV-2”:

Overview The study investigated the infection of T lymphocytes by SARS-CoV-2 and whether it contributes to lymphopenia (reduced lymphocyte count) observed in severe COVID-19 cases. It was discovered that SARS-CoV-2 can infect T lymphocytes, particularly CD4+ T cells, in an ACE2-independent manner, which is a significant departure from the previously understood mechanism of the virus entering cells​​.

Key Findings

  1. Presence of SARS-CoV-2 in Lymphocytes: The study found SARS-CoV-2 viral antigens in peripheral blood cells and lung T cells of COVID-19 patients, confirming that T lymphocytes are targeted by the virus. A significant reduction in T lymphocyte populations, especially CD4+ and CD8+ T cells, was noted in patients compared to healthy individuals​​.
  2. In Vitro Infection of T Cells: Laboratory experiments using T cell lines and primary T cells from healthy donors showed that SARS-CoV-2 can infect these cells. The infection was more pronounced in activated T cells, and it led to the accumulation of viral RNA and proteins inside the cells​​.
  3. Independence from ACE2 and TMPRSS2: Contrary to the common entry mechanism of SARS-CoV-2 through ACE2 receptors and TMPRSS2 protein, the study demonstrated that the virus infects T cells in an ACE2-independent manner. This was shown by the lack of effect of ACE2 and TMPRSS2 inhibitors on the infection of T cells by the virus​​.
  4. Induction of T-Cell Death: SARS-CoV-2 infection in T cells was found to trigger significant cell death. The study used apoptosis assays to demonstrate that T cells from COVID-19 patients and those infected in vitro showed a marked increase in apoptosis. This could contribute to the lymphopenia observed in severe COVID-19 cases​​.
  5. Potential Receptors in T Cells: The study explored various potential receptors for SARS-CoV-2 infection in T cells. It identified LFA-1 (leukocyte function-associated antigen-1) as a likely candidate facilitating the virus’s entry into T cells. Experiments showed that overexpression of LFA-1 in T cells increased susceptibility to SARS-CoV-2 infection, while its inhibition reduced the viral load​​.

Implications The discovery of an ACE2-independent pathway for SARS-CoV-2 infection in T cells challenges the current understanding of how the virus interacts with the human immune system. It underscores the complexity of the virus’s interaction with the immune system and highlights the need for further research in developing effective treatments for COVID-19. The study also indicates that targeting the LFA-1 pathway could be a potential therapeutic strategy to prevent virus-induced lymphopenia and its associated complications in COVID-19 patients​​.

Read More: https://www.nature.com/articles/s41392-022-00919-x

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