Title : Endosomal TLRs may have no important effect on higher transmissibility of SARS CoV 2 alpha and delta variants
Abstract:
Toll-like receptors (TLRs) are essential for activation of innate immunity and initiation of adaptive immune response. They have been associated with several respiratory diseases, but information on the relation of TLRs with SARS-CoV-2 still needs to be completed. Endosomal TLRs can detect viral or bacterial nucleic acids and have an important role in initiation of immune responses against the pathogens. TLR7/8 can detect consecutive uridine-containing single-stranded RNA of the viral genome. TLR9 binds CpG signaling motifs in bacterial and viral DNA molecules, and is found to be highly expressed in peripheral blood mononuclear cells after infection with SARS-CoV. Also, the SARS-CoV genome has higher numbers of TLR9 signaling motifs than some other respiratory diseases viruses. It was shown that SARS-CoV-2 genome has more TLR7/8-detectable motifs than SARS-CoV genome, representing a higher probability to interact with TLR7/8. This was linked to the potential ability of SARS-CoV-2 to induce pro-inflammatory responses in severe lung injury cases. Since it was shown that alpha and delta variants are associated with higher transmission rates, in this study, we performed a bioinformatic analysis on the interaction of endosomal TLRs and SARS-CoV-2 wild type, alpha and delta variants. We used Sequence Searcher software for searching TLR7/TLR8 RNA motifs, and TLR9 CpG motif in the SARS-CoV-2 genome of Wuhan reference sequence and alpha and delta variants. Data analysis showed that the overall number of genomic motifs detectable by TLR7/8/9 in SARS-CoV-2 alpha and delta variants was lower than in SARS-CoV-2 wild type sequence. This suggests that the endosomal TLRs may have no important effect on higher transmissibility of SARS-CoV-2 alpha and delta variants. Also, lower detectable motifs in delta than alpha variant, indicated a potential lower binding affinity to endosomal TLRs compared with alpha. As a conclusion, higher transmission rates reported for alpha and delta variants may not be due to the genomic mutations that alter the number of TLR7/8/9-detectable motifs.
