tetano
Editor, Senior Moderator
Cell Rep Med
. 2024 Jan 16;5(1):101362.
doi: 10.1016/j.xcrm.2023.101362. Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells
Dong-Il Kwon[SUP] 1 [/SUP], Subin Park[SUP] 1 [/SUP], Yujin L Jeong[SUP] 1 [/SUP], Young-Min Kim[SUP] 1 [/SUP], Jeongyong Min[SUP] 1 [/SUP], Changhyung Lee[SUP] 1 [/SUP], Jung-Ah Choi[SUP] 2 [/SUP], Yoon Ha Choi[SUP] 1 [/SUP], Hyun-Jung Kong[SUP] 3 [/SUP], Youngwon Choi[SUP] 3 [/SUP], Seungtae Baek[SUP] 4 [/SUP], Kun-Joo Lee[SUP] 1 [/SUP], Yeon-Woo Kang[SUP] 1 [/SUP], Chaerim Jeong[SUP] 1 [/SUP], Gihoon You[SUP] 1 [/SUP], Youngsik Oh[SUP] 1 [/SUP], Sun-Kyoung Im[SUP] 4 [/SUP], Manki Song[SUP] 2 [/SUP], Jong Kyoung Kim[SUP] 1 [/SUP], Jun Chang[SUP] 3 [/SUP], Donghoon Choi[SUP] 5 [/SUP], Seung-Woo Lee[SUP] 6 [/SUP]
Affiliations
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 long-acting 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 γ (IFNγ)+ 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 IAV- and 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.
Keywords: SARS-CoV-2; influenza A virus; innate-like T cells; interleukin-17A; interleukin-7; virus infection.
. 2024 Jan 16;5(1):101362.
doi: 10.1016/j.xcrm.2023.101362. Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells
Dong-Il Kwon[SUP] 1 [/SUP], Subin Park[SUP] 1 [/SUP], Yujin L Jeong[SUP] 1 [/SUP], Young-Min Kim[SUP] 1 [/SUP], Jeongyong Min[SUP] 1 [/SUP], Changhyung Lee[SUP] 1 [/SUP], Jung-Ah Choi[SUP] 2 [/SUP], Yoon Ha Choi[SUP] 1 [/SUP], Hyun-Jung Kong[SUP] 3 [/SUP], Youngwon Choi[SUP] 3 [/SUP], Seungtae Baek[SUP] 4 [/SUP], Kun-Joo Lee[SUP] 1 [/SUP], Yeon-Woo Kang[SUP] 1 [/SUP], Chaerim Jeong[SUP] 1 [/SUP], Gihoon You[SUP] 1 [/SUP], Youngsik Oh[SUP] 1 [/SUP], Sun-Kyoung Im[SUP] 4 [/SUP], Manki Song[SUP] 2 [/SUP], Jong Kyoung Kim[SUP] 1 [/SUP], Jun Chang[SUP] 3 [/SUP], Donghoon Choi[SUP] 5 [/SUP], Seung-Woo Lee[SUP] 6 [/SUP]
Affiliations
- PMID: 38232693
- DOI: 10.1016/j.xcrm.2023.101362
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 long-acting 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 γ (IFNγ)+ 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 IAV- and 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.
Keywords: SARS-CoV-2; influenza A virus; innate-like T cells; interleukin-17A; interleukin-7; virus infection.