Xin Wang, Feiyang Pu, Xuanye Yang, Xili Feng, Jiayou Zhang, Kai Duan, Xuanxuan Nian, Zhongren Ma, Xiao-Xia Ma, Xiao-Ming Yang
{"title":"免疫抑制剂通过抑制核酸合成、mRNA剪接和蛋白质稳定性对甲型 H1N1 pdm09 流感病毒产生抗病毒作用。","authors":"Xin Wang, Feiyang Pu, Xuanye Yang, Xili Feng, Jiayou Zhang, Kai Duan, Xuanxuan Nian, Zhongren Ma, Xiao-Xia Ma, Xiao-Ming Yang","doi":"10.1080/21505594.2023.2301242","DOIUrl":null,"url":null,"abstract":"<p><p>Influenza A virus (IAV) poses a threat to patients receiving immunosuppressive medications since they are more susceptible to infection with severe symptoms, and even death. Understanding the direct effects of immunosuppressants on IAV infection is critical for optimizing immunosuppression in these patients who are infected or at risk of influenza virus infection. We profiled the effects of 10 immunosuppressants, explored the antiviral mechanisms of immunosuppressants, and demonstrated the combined effects of immunosuppressants with the antiviral drug oseltamivir in IAV-infected cell models. We found that mycophenolic acid (MPA) strongly inhibits viral RNA replication via depleting cellular guanosine pool. Treatment with 6-Thioguanine (6-TG) promoted viral protein degradation through a proteasomal pathway. Filgotinib blocked mRNA splicing of matrix protein 2, resulting in decreased viral particle assembly. Furthermore, combined treatment with immunosuppressants and oseltamivir inhibits IAV viral particle production in an additive or synergic manner. Our results suggest that MPA, 6-TG, and filgotinib could be the preferential choices for patients who must take immunosuppressants but are at risk of influenza virus infection.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854267/pdf/","citationCount":"0","resultStr":"{\"title\":\"Immunosuppressants exert antiviral effects against influenza A(H1N1)pdm09 virus via inhibition of nucleic acid synthesis, mRNA splicing, and protein stability.\",\"authors\":\"Xin Wang, Feiyang Pu, Xuanye Yang, Xili Feng, Jiayou Zhang, Kai Duan, Xuanxuan Nian, Zhongren Ma, Xiao-Xia Ma, Xiao-Ming Yang\",\"doi\":\"10.1080/21505594.2023.2301242\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Influenza A virus (IAV) poses a threat to patients receiving immunosuppressive medications since they are more susceptible to infection with severe symptoms, and even death. Understanding the direct effects of immunosuppressants on IAV infection is critical for optimizing immunosuppression in these patients who are infected or at risk of influenza virus infection. We profiled the effects of 10 immunosuppressants, explored the antiviral mechanisms of immunosuppressants, and demonstrated the combined effects of immunosuppressants with the antiviral drug oseltamivir in IAV-infected cell models. We found that mycophenolic acid (MPA) strongly inhibits viral RNA replication via depleting cellular guanosine pool. Treatment with 6-Thioguanine (6-TG) promoted viral protein degradation through a proteasomal pathway. Filgotinib blocked mRNA splicing of matrix protein 2, resulting in decreased viral particle assembly. Furthermore, combined treatment with immunosuppressants and oseltamivir inhibits IAV viral particle production in an additive or synergic manner. Our results suggest that MPA, 6-TG, and filgotinib could be the preferential choices for patients who must take immunosuppressants but are at risk of influenza virus infection.</p>\",\"PeriodicalId\":23747,\"journal\":{\"name\":\"Virulence\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854267/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Virulence\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/21505594.2023.2301242\",\"RegionNum\":1,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virulence","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/21505594.2023.2301242","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Immunosuppressants exert antiviral effects against influenza A(H1N1)pdm09 virus via inhibition of nucleic acid synthesis, mRNA splicing, and protein stability.
Influenza A virus (IAV) poses a threat to patients receiving immunosuppressive medications since they are more susceptible to infection with severe symptoms, and even death. Understanding the direct effects of immunosuppressants on IAV infection is critical for optimizing immunosuppression in these patients who are infected or at risk of influenza virus infection. We profiled the effects of 10 immunosuppressants, explored the antiviral mechanisms of immunosuppressants, and demonstrated the combined effects of immunosuppressants with the antiviral drug oseltamivir in IAV-infected cell models. We found that mycophenolic acid (MPA) strongly inhibits viral RNA replication via depleting cellular guanosine pool. Treatment with 6-Thioguanine (6-TG) promoted viral protein degradation through a proteasomal pathway. Filgotinib blocked mRNA splicing of matrix protein 2, resulting in decreased viral particle assembly. Furthermore, combined treatment with immunosuppressants and oseltamivir inhibits IAV viral particle production in an additive or synergic manner. Our results suggest that MPA, 6-TG, and filgotinib could be the preferential choices for patients who must take immunosuppressants but are at risk of influenza virus infection.
期刊介绍:
Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication.
Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.