AI Article Synopsis
- - Respiratory syncytial virus (RSV) is a major cause of lung infections in infants and the elderly, but there are currently no specific treatments for it.
- - Researchers tested Axl inhibitors, which block a receptor involved in regulating the immune response, and found that they significantly reduced RSV infection in both cell cultures and animal models.
- - The study suggests that Axl inhibitors can enhance the body’s antiviral response, leading to increased immune activity and a reduction in virus levels and inflammation in the lungs.
Article Abstract
Respiratory syncytial virus (RSV) infection persists as a common pathogen of pulmonary infection in infants and in the elderly with high morbidity and mortality. However, no specific therapeutics are available. Axl, a member of the TAM (Tyro3, Axl, and Mertk) family receptor kinases, is a pleiotropic inhibitor of the innate immune response and functions as a negative regulator of interferon pathway activation. In this report, we investigated Axl inhibitors for their effects against RSV infection. Axl inhibition with kinase inhibitors, including BMS-777607, R428, and TP-0903, or Axl ablation resulted in a significant reduction of RSV infection in cell-based assays. In an animal model of pulmonary RSV infection, treatment with BMS-777607, R428, or TP-0903 ameliorated pulmonary pathology with a significant reduction of RSV titers in the lung tissues and, consequently, decreased the expression of proinflammatory genes. The host promotes ISG expression for the antiviral response and for viral clearance. We found that Axl inhibition led to more robust IFN-β expression and antiviral gene induction. Thus, the results of this study imply that Axl kinase inhibitors may possess a broad spectrum of antiviral effects by promoting ISG expression.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019287 | PMC |
| http://dx.doi.org/10.1128/aac.01487-22 | DOI Listing |
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