Title: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
Volume: 27
Issue: 44
Author(s): Khalid Alshaghdali, Mohd Saeed*, Mohammad Amjad Kamal and Amir Saeed*
Affiliation:
- Department of Biology, College of Sciences, University of Hail, Hail,Saudi Arabia
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail,Saudi Arabia
Keywords:
RSV, TLRs, RSV G protein, TNF-α, IL-6, TLR2, TLR4.
Abstract:
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.
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.
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.
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.
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.