Acquired Immune Deficiency Syndrome correlation with SARS-CoV-2 N genotypes

The study “Acquired Immune Deficiency Syndrome correlation with SARS-CoV-2 N genotypes” explores the potential for certain SARS-CoV-2 genotypes to induce an acquired immune deficiency syndrome (AIDS) by infecting lymphocytes.

Here’s a detailed summary:

Background and Hypothesis:

  • The study hypothesizes that the N protein of SARS-CoV-2, unlike the spike protein, may infect lymphocytes, inducing their death and drastically reducing their population. This mechanism could lead to serious immune deficiency, allowing the virus to remain hidden for long periods, contributing to Long-Covid Disease​​.

Methodology:

  • The research involved a computational assay analyzing sequences from GISAID to correlate N genotypes with an enhancement in affinity for certain receptors in lymphocytes.

Key Findings:

  1. Lymphopenia in COVID-19 Patients: Lymphopenia, a major immunological abnormality in severe COVID-19 patients, causes general immunosuppression and facilitates viral persistence. Clinical data suggests it is mainly related to viral infections and can occur due to various molecular and cellular mechanisms​​.
  2. Infection of Lymphocytes by SARS-CoV-2: The study found that SARS-CoV-2 can infect lymphocytes. Specifically, the viroporin 3a (ORF3a) of the virus interacts with NLRP3, causing pyroptosis – a form of programmed cell death. This interaction might worsen lymphopenia and contribute to the dysfunction of adaptive immunity in COVID-19​​.
  3. Interaction with CD147: Both the N protein (N-RBD) and the spike receptor-binding domain (S-RBD) of SARS-CoV-2 can bind to CD147, a transmembrane glycoprotein. This interaction is crucial for the virus’s ability to infect lymphocytes and induce immune deficiency​​.
  4. Genotypes N/120 and N/152: The study identified genotypes N/120 and N/152 as key in reducing the immune response of the host. These genotypes allow the virus to persist indefinitely, causing an acquired immune deficiency syndrome​​.
  5. S Protein Affinity Changes: Improvements in the affinity of the S protein with CD147 compromise its affinity with the ACE2 receptor, which is vital for the virus to infect host cells. This change affects the virus’s ability to infect lymphocytes and other cells​​.
  6. Implications of Genotype Optimization: The study notes that optimizing genotypes S/493 and S/484 improves airborne spread by infecting more the lungs and nasopharyngeal tissue. Meanwhile, N/120 and N/152 genotypes reduce the immune response, facilitating viral persistence and causing AIDS and related syndromes​​.

Conclusion:

  • The study concludes that certain SARS-CoV-2 genotypes, particularly N/120 and N/152, have the potential to cause an acquired immune deficiency syndrome by infecting lymphocytes. This finding has significant implications for understanding the long-term effects of COVID-19 and the development of therapeutic strategies.

Read More: https://www.sciencedirect.com/science/article/pii/S2319417023000872

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