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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

Author(s):

Khalid Alshaghdali, Mohd Saeed*, Mohammad Amjad Kamal and Amir Saeed*  

Abstract:


Background: The human respiratory syncytial virus (RSV) has been linked with various respiratory diseases such as common cold to lower respiratory tract illnesses like pneumonia and bronchiolitis. TLRs play a critical role in generating host immune responses 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 an 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.

Objective: We hypothesized that RSV G protein could 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.

Methods: Different TLR antagonists were used to assessing the effect of RSV and RSV G ectodomain exposure 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.

Results: 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 the binding and activating TLR2/TLR6 signaling.

Conclusion: In summary, our study shows that TLR2/TLR6 plays an essential role in activating an innate immune response upon RSV recognition, which could help promote RSV clearance and preventing RSV-induced disease.

Keywords:

RSV, TLRs, RSV G protein, TNF-α, IL-6, TLR2, TLR4

Affiliation:

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Department of Biology, College of Sciences, University of Hail, Hail, King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail



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