Interaction of Ectodomain of Respiratory Syncytial Virus G Protein with TLR2/ TLR6 Heterodimer: An In vitro and In silico Approach to Decipher the Role of RSV G Protein in Pro-inflammatory Response against the Virus

呼吸道合胞病毒 G 蛋白胞外域与 TLR2/TLR6 异二聚体的相互作用:一种体外和计算机模拟方法来揭示 RSV G 蛋白在抗病毒促炎反应中的作用

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作者:Khalid Alshaghdali, Mohd Saeed, Mohammad Amjad Kamal, Amir Saeed

Background

Human respiratory syncytial virus (RSV) has been shown to be linked with various forms of respiratory diseases, such as common cold and lower respiratory tract illnesses like pneumonia and bronchiolitis. TLRs play critical role in generating host immune response against RSV. TLRs are expressed not only on leukocytes but also on many other cell types and can recognize RSV. Previous studies have established that RSV can interact with TLR4 and initiate inflammatory cascade of cytokines. The data from a recent study indicated that TLR2/TLR6 is involved in RSV recognition and subsequent innate immune activation. However, the nature of binding and the envelope protein of RSV involved in this interaction with TLRs are not studied yet.

Conclusion

In summary, our study shows that TLR2/TLR6 play important role in the activation of innate immune response upon RSV recognition which could be helpful in promoting RSV clearance and preventing RSV-induced disease.

Methods

Different TLR antagonists were used to assess the effect of the exposure of RSV and RSV G ectodomain in human primary small airway epithelial cells (HSAECs). Various inflammatory cytokines, chemokines and type I IFNs were measured by ELISA along with their mRNA expression by qPCR. In silico interaction of RSV G protein with TLR2/TLR6 was also analyzed.

Objective

We hypothesized that RSV G protein can bind to TLRs and mediate the inflammatory immune response against the virus infection. Therefore, we investigated whether RSV G protein could activate innate immune response through TLR signaling.

Results

Results of ELISA and qPCR analysis have shown that TLR2/TLR6 signaling is activated in HSAECs upon RSV and RSV G protein exposure which initiates innate immune response against RSV. Moreover, RSV envelope protein G plays a crucial role in binding and activation of TLR2/TLR6 signaling.

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