Ya-Fang Mei: Department of Clinical Microbiology, Virology, Umeå University, SE-90185 Umeå, Sweden
Viruses 2021, 13(10), 2056;
https://doi.org/10.3390/v13102056
Published: 13 October 2021
"Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS–CoV–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. ...
4. Discussion
Our findings provide evidence of the spike protein hijacking the DNA damage repair machinery and adaptive immune machinery in vitro.
We propose 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, our in vitro V(D)J reporter assay shows that the spike protein intensely impeded V(D)J recombination.
Consistent with our results, 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 ris].
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, our data provide valuable details on the involvement of spike protein subunits in DNA damage repair,
indicating that full–length spike–based vaccines 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.
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, we identified one of the potentially important mechanisms of SARS–CoV–2 suppression of the host adaptive immune machinery.
Furthermore, our 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."
Tuesday, December 7, 2021
"SARS–CoV–2 Spike Impairs DNA Damage Repair"
Authors:
Hui Jiang: Department of Molecular Biosciences, The Wenner–Gren Institute, Stockholm University, SE-10691 Stockholm, Sweden
