Axl Mediates Resistance to Respiratory Syncytial Virus Infection Independent of Cell Attachment

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants and young children. Axl, a TAM family receptor tyrosine kinase, has been demonstrated to be a receptor mediating enveloped virus infection. Here we show that Axl functions as a suppressor of antiviral response during RSV infection. Knockdown of Axl expression in human cells resulted in cell resistance to RSV infection, although the treatment did not significantly affect RSV binding or cell entry. Mice deficient in Axl showed resistance to RSV infection, including reduction in viral load and in pulmonary injury. Although T lymphocyte and macrophage infiltration was reduced, more IFN-gamma-producing cells were present in BAL fluid in Axl(-/-) mice. Fewer alternatively activated alveolar macrophages were found in the lungs of Axl(-/-) mice. Axl(-/-) mouse embryonic fibroblasts and siRNA-treated human cells had more robust IFN-beta and IFN-stimulated gene induction of antiviral genes. Furthermore, reexpression of Axl using adenovirus-mediated Axl delivery repressed IFN-stimulated gene induction in Axl-null mouse embryonic fibroblasts by RSV infection. The results suggest that Axl, independent of being a virus entry receptor of RSV infection, negatively regulates IFN signaling to modulate host antiviral response against RSV infection.

Automated summary

This study found that Axl acts as a suppressor of the antiviral response during RSV infection by negatively regulating IFN signaling.