Study On The Antiviral Role Mediated By Toll-like Receptor7in Balb/c Mice Infected With Respiratory Syncytial Virus

Objective: To investigate the expression changes of Toll-like receptor7(TLR7) mRNAand protein in lung tissue of BALB/c mice infected with respiratory syncytial virus(RSV), and to explore the antiviral role of type I interferon and regulatory mechanismmediated by TLR7activation. In order to provide original idea for the prevention andclinical therapy of RSV infection.Methods: RSV-infected BALB/c mice were pretreated with or without specific agonistof TLR7, and the lung tissues were harvested at the selected time points after RSVinfection (4,8,12and24h, respectively). The uninfected BALB/c mice were asnormal controls. Lung tissue sections were stained with hematoxylin and eosin, andexamined under a light microscope for histopathological examination. The expressionof TLR7、IRF3/7、IFN-α/β and RSV F gene mRNA were evaluated semiquantitativelyby RT-PCR. The expression of TLR7was detected by Western-Blot. The viral titers inlung tissue homogenate were measured by plaque forming unit (PFU) assay.Results:①HE staining showed pulmonary inflammation in RSV-infected mice washeavier along with the infection progress, but the TLR7agonist treatment couldmarkedly attenuate the pulmonary inflammation;②RSV infection could up-regulate theexpression of TLR7mRNA in a time-dependent manner, and those of IRF3, IRF7,IFN-α, IFN-β and RSV F mRNA levels also rose in infected lung tissue. The changessignificantly compared with the control group. Pretreatment of TLR7with specificagonist Imiquimod, whereas, significantly up-regulate the activation of TLR7. the expression of IRF7, IFN-α mRNA are also increased obviously, and the expression ofthem are more increased obviously than IRF3and IFN-β, but the expression of RSV FmRNA descented gradually;③It was found that RSV infection could up-regulate theexpression of TLR7protien in a time-dependent manner，but in Imiquimod treatmentgroup the expression of TLR7protein increased more markedly than RSV-infectedgroup;④RSV-infected could significantly increase the rate of viral replication titer inthe lung tissue homogenate in a time-dependent manner, however, in Imiquimod treatedgroup the viral replication titer in lung tissue homogenate reduced more obviously thanRSV-infected group.Conclusions: Type I interferon produced mediated by TLR7in BALB/c mice infectedwith RSV. Interferon are increased by pretreatment of TLR7specific agonistImiquimod, but the expression of RSV F mRNA and the viral replication titer in lungtissue homogenat descented obviously, and the pulmonary inflammation also attenuated.It suggests that the antiviral mechanism was related with TLR7transducing pathway inRSV-infected BALB/c mice lung tissue, and TLR7was mainly induced IFN-α of type Iinterferon via IRF7.