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Source: SARS-CoV-2 Research  Nov 01, 2021  3 months ago
BREAKING! Swedish Study Shows That SARS–CoV–2 Spike Impairs DNA Damage Repair And Inhibits V(D)J Recombination In Vitro. Implications For Vaccines As Well!
BREAKING! Swedish Study Shows That SARS–CoV–2 Spike Impairs DNA Damage Repair And Inhibits V(D)J Recombination In Vitro. Implications For Vaccines As Well!
Source: SARS-CoV-2 Research  Nov 01, 2021  3 months ago
SARS-CoV-2 Research: A new breakthrough vitro study by researchers from Department of Molecular Biosciences of the Wenner–Gren Institute-Stockholm University and also from the Department of Clinical Microbiology, Virology-Umeå University has found that the SARS-CoV-2 Spike proteins not only impairs DNA repair in the cells of the infected human host but that it also inhibits V(D)J recombination.

V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors found in B cells and T cells, respectively.
The SARS–CoV–2 or severe acute respiratory syndrome coronavirus 2 has led to the coronavirus disease 2019 (COVID–19) pandemic, severely affecting public health and the global economy.
Adaptive immunity plays a crucial role in fighting against SARS–CoV–2 infection and directly influences the clinical outcomes of patients. Clinical studies have indicated that patients with severe COVID–19 exhibit delayed and weak adaptive immune responses; however, the mechanism by which SARS–CoV–2 impedes adaptive immunity remains unclear.
The study team using an in vitro cell line, report that the SARS–CoV–2 spike protein significantly inhibits DNA damage repair, which is required for effective V(D)J recombination in adaptive immunity. Mechanistically, the study team found that the spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site.
The study findings reveal a potential molecular mechanism by which the spike protein might impede adaptive immunity and underscore the potential side effects of full-length spike-based vaccines.
The study findings were published in the peer reviewed journal: Viruses https://www.mdpi.com/1999-4915/13/10/2056/htm
The SARS-CoV-2 Research findings provide evidence of the spike protein hijacking the DNA damage repair machinery and adaptive immune machinery in vitro. The study team proposes a potential mechanism by which spike proteins may impair adaptive immunity by inhibiting DNA damage repair. Although no evidence has been published that SARS–CoV–2 can infect thymocytes or bone marrow lymphoid cells, the in vitro V(D)J reporter assay shows that the spike protein intensely impeded V(D)J recombination.
Consistent with these new findings, clinical observations also show that the risk of severe illness or death with COVID–19 increases with age, especially older adults who are at the highest risk. This may be because SARS–CoV–2 spike proteins can weaken the DNA repair system of older people and consequently impede V(D)J recombination and adaptive immunity.
In contrast, the study data provide valuable details on the involvement of spike protein subunits in DNA damage repair, indicating that full–length spike–based vacci nes may inhibit the recombination of V(D)J in B cells, which is also consistent with a recent study that a full–length spike–based vaccine induced lower antibody titers compared to the RBD–based vaccine. https://pubmed.ncbi.nlm.nih.gov/33693030/
This suggests that the use of antigenic epitopes of the spike as a SARS–CoV–2 vaccine might be safer and more efficacious than the full–length spike. Taken together, the study team identified one of the potentially important mechanisms of SARS–CoV–2 suppression of the host adaptive immune machinery.
Furthermore, the study findings also imply a potential side effect of the full–length spike–based vaccine. This work will improve the understanding of COVID–19 pathogenesis and provide new strategies for designing more efficient and safer vaccines.
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Feb 05, 2020  2 years ago
Source : Thailand Medical news