The economical role of RIOK3 in modulating the Jak1/STAT1 pathway and antiviral immunity against respiratory syncytial virus infection in macrophages: implications for therapeutic potential
Respiratory Syncytial Virus (RSV) is a leading cause of lower respiratory tract infections, particularly in vulnerable populations such as infants, the elderly, and immunocompromised individuals. RSV infection can result in mortality rates as high as 20%, attributable not only to viral replication b...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1591473/full |
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| author | Fangfang Sun Fangfang Sun Weiwei Liang Yingying Qian Pengfei Hu Pengfei Hu |
| author_facet | Fangfang Sun Fangfang Sun Weiwei Liang Yingying Qian Pengfei Hu Pengfei Hu |
| author_sort | Fangfang Sun |
| collection | DOAJ |
| description | Respiratory Syncytial Virus (RSV) is a leading cause of lower respiratory tract infections, particularly in vulnerable populations such as infants, the elderly, and immunocompromised individuals. RSV infection can result in mortality rates as high as 20%, attributable not only to viral replication but also to an excessive host immune response. Current therapeutic options are limited, partly due to gaps in understanding the host immune response, especially the role of macrophages and their signaling pathways. This study investigates the role of RIOK3, an unconventional kinase, in modulating the Jak1/STAT1 pathway during RSV infection in macrophages and its impact on viral replication and interferon production. Using both in vitro and in vivo models, including primary bone marrow-derived macrophages (BMM) from control and RIOK3 knockout (KO) mice, we demonstrate that RIOK3 is a critical regulator of the Jak1/STAT1 pathway in macrophages during RSV infection. The absence of RIOK3 enhances viral replication and disrupts the balance of type I interferons. Targeting RIOK3 may represent a promising strategy to enhance antiviral immunity and mitigate RSV-induced inflammation, thus warranting further investigation for therapeutic potential. |
| format | Article |
| id | doaj-art-8a44889da5f34b6e982dffd7010cf259 |
| institution | OA Journals |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-8a44889da5f34b6e982dffd7010cf2592025-08-20T02:28:46ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-04-011610.3389/fmicb.2025.15914731591473The economical role of RIOK3 in modulating the Jak1/STAT1 pathway and antiviral immunity against respiratory syncytial virus infection in macrophages: implications for therapeutic potentialFangfang Sun0Fangfang Sun1Weiwei Liang2Yingying Qian3Pengfei Hu4Pengfei Hu5Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaCancer Center, Zhejiang University, Hangzhou, ChinaDepartment of Endocrinology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Geriatrics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaOrthopedics Research Institute of Zhejiang University, Hangzhou, ChinaRespiratory Syncytial Virus (RSV) is a leading cause of lower respiratory tract infections, particularly in vulnerable populations such as infants, the elderly, and immunocompromised individuals. RSV infection can result in mortality rates as high as 20%, attributable not only to viral replication but also to an excessive host immune response. Current therapeutic options are limited, partly due to gaps in understanding the host immune response, especially the role of macrophages and their signaling pathways. This study investigates the role of RIOK3, an unconventional kinase, in modulating the Jak1/STAT1 pathway during RSV infection in macrophages and its impact on viral replication and interferon production. Using both in vitro and in vivo models, including primary bone marrow-derived macrophages (BMM) from control and RIOK3 knockout (KO) mice, we demonstrate that RIOK3 is a critical regulator of the Jak1/STAT1 pathway in macrophages during RSV infection. The absence of RIOK3 enhances viral replication and disrupts the balance of type I interferons. Targeting RIOK3 may represent a promising strategy to enhance antiviral immunity and mitigate RSV-induced inflammation, thus warranting further investigation for therapeutic potential.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1591473/fullRSVmacrophageRIOK3Jak1/STAT pathwaytype I interferon |
| spellingShingle | Fangfang Sun Fangfang Sun Weiwei Liang Yingying Qian Pengfei Hu Pengfei Hu The economical role of RIOK3 in modulating the Jak1/STAT1 pathway and antiviral immunity against respiratory syncytial virus infection in macrophages: implications for therapeutic potential Frontiers in Microbiology RSV macrophage RIOK3 Jak1/STAT pathway type I interferon |
| title | The economical role of RIOK3 in modulating the Jak1/STAT1 pathway and antiviral immunity against respiratory syncytial virus infection in macrophages: implications for therapeutic potential |
| title_full | The economical role of RIOK3 in modulating the Jak1/STAT1 pathway and antiviral immunity against respiratory syncytial virus infection in macrophages: implications for therapeutic potential |
| title_fullStr | The economical role of RIOK3 in modulating the Jak1/STAT1 pathway and antiviral immunity against respiratory syncytial virus infection in macrophages: implications for therapeutic potential |
| title_full_unstemmed | The economical role of RIOK3 in modulating the Jak1/STAT1 pathway and antiviral immunity against respiratory syncytial virus infection in macrophages: implications for therapeutic potential |
| title_short | The economical role of RIOK3 in modulating the Jak1/STAT1 pathway and antiviral immunity against respiratory syncytial virus infection in macrophages: implications for therapeutic potential |
| title_sort | economical role of riok3 in modulating the jak1 stat1 pathway and antiviral immunity against respiratory syncytial virus infection in macrophages implications for therapeutic potential |
| topic | RSV macrophage RIOK3 Jak1/STAT pathway type I interferon |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1591473/full |
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