Does COVID-19 suppress the immune response?
According to the publication in Nature (https://www.nature.com/articles/s41591-020-0820-9), the spike protein of SARS-CoV-2 has a polybasic cleavage site due to an insertion of 12 nucleotides at the region encoding the junction of S1 and S2 subunits. “This allows effective cleavage by furin and other proteases and has a role in determining viral infectivity and host range”.
Comparing the sequences of the bat coronavirus RaTG13 and Wuhan-Hu-1 (COVID-19) around this site shows the regions of sequence similarity and the insertion itself (see below). What we found interesting is that the inserted sequence and a few flanking nucleotides form a perfect 16 bp anti-sense match to the human BLNK gene that plays a critical role in B cell development (https://www.genecards.org/cgi-bin/carddisp.pl?gene=BLNK).
Sequences from human BLNK (top), COVID-19 and bat coronavirus (bottom) are aligned. The sequence of insertion in COVID-19 spike protein-coding gene matches a region in BLNK gene at the location known to have mutations leading to agammaglobulinemia. The solid ribbons connect identical sequences.
Notably, the matching region contains known ClinVar mutations that cause agammaglobulinemia resulting in serial bacterial infections due to failures in specific immune responses because of defects in B-lymphocytes. We realize that the size of the matching region does not result in a good statistical significance of the match (evalue=20). At the same time, this is the only perfect match for the insertion sequence that we could find in the human genome. Plus, the 16-base sequence has high GC content, which should make the potential RNA duplex more stable. Could it be that COVID-19 also suppresses the immune response by silencing the expression of BLNK gene? We would like to hear from experts.
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