tetano
Editor, Senior Moderator
Virology. 2019 Nov 5;540:17-22. doi: 10.1016/j.virol.2019.11.003. [Epub ahead of print] [h=1]IFITM3 and type I interferons are important for the control of influenza A virus replication in murine macrophages.[/h]
Londrigan SL[SUP]1[/SUP], Wakim LM[SUP]2[/SUP], Smith J[SUP]2[/SUP], Haverkate AJ[SUP]2[/SUP], Brooks AG[SUP]2[/SUP], Reading PC[SUP]3[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Victoria, 3000, Australia. Electronic address: sarahll@unimelb.edu.au. 2 Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Victoria, 3000, Australia. 3 Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Victoria, 3000, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Victoria, 3000, Australia.
[h=3]Abstract[/h] Abortive infection of macrophages serves as a "dead end" for most seasonal influenza A virus (IAV) strains, and it is likely to contribute to effective host defence. Interferon (IFN)-induced transmembrane protein 3 (IFITM3) restricts the early stages of IAV replication in epithelial cells, but IFITM3 restriction of IAV replication in macrophages has not been previously investigated. Herein, macrophages isolated from IFITM3-deficient mice were more susceptible to initial IAV infection, but late-stage viral replication was still controlled through abortive infection. Strikingly, IFNα/β receptor (IFNAR)-deficient macrophages infected with IAV were not only more susceptible to initial infection, but these cells also supported productive viral replication. Significantly, we have established that abortive IAV infection in macrophages is controlled through a type I IFN-dependent mechanism, where late-stage IAV replication can proceed in the absence of type I IFN responses. These findings provide novel mechanistic insight into macrophage-specific processes that potently shut down IAV replication.
Copyright ? 2019. Published by Elsevier Inc.
[h=4]KEYWORDS:[/h] IFITM3; Influenza; Interferon stimulated genes; Macrophages; Type I interferon; Viral restriction factors
PMID: 31731106 DOI: 10.1016/j.virol.2019.11.003
Londrigan SL[SUP]1[/SUP], Wakim LM[SUP]2[/SUP], Smith J[SUP]2[/SUP], Haverkate AJ[SUP]2[/SUP], Brooks AG[SUP]2[/SUP], Reading PC[SUP]3[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Victoria, 3000, Australia. Electronic address: sarahll@unimelb.edu.au. 2 Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Victoria, 3000, Australia. 3 Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Victoria, 3000, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Victoria, 3000, Australia.
[h=3]Abstract[/h] Abortive infection of macrophages serves as a "dead end" for most seasonal influenza A virus (IAV) strains, and it is likely to contribute to effective host defence. Interferon (IFN)-induced transmembrane protein 3 (IFITM3) restricts the early stages of IAV replication in epithelial cells, but IFITM3 restriction of IAV replication in macrophages has not been previously investigated. Herein, macrophages isolated from IFITM3-deficient mice were more susceptible to initial IAV infection, but late-stage viral replication was still controlled through abortive infection. Strikingly, IFNα/β receptor (IFNAR)-deficient macrophages infected with IAV were not only more susceptible to initial infection, but these cells also supported productive viral replication. Significantly, we have established that abortive IAV infection in macrophages is controlled through a type I IFN-dependent mechanism, where late-stage IAV replication can proceed in the absence of type I IFN responses. These findings provide novel mechanistic insight into macrophage-specific processes that potently shut down IAV replication.
Copyright ? 2019. Published by Elsevier Inc.
[h=4]KEYWORDS:[/h] IFITM3; Influenza; Interferon stimulated genes; Macrophages; Type I interferon; Viral restriction factors
PMID: 31731106 DOI: 10.1016/j.virol.2019.11.003