Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells

Abstract

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of longacting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood -derived interferon g (IFNg)+ conventional T cells and locally expanded IL -17A+ innate -like T cells. Single -cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate -like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL -17A in both IAVand SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.