Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection

James G Bedford; Meredith O'Keeffe; Patrick C Reading; Linda M Wakim

doi:10.1371/journal.pone.0210132

Rapid interferon independent expression of IFITM3 following T cell activation protects cells from influenza virus infection

PLoS One. 2019 Jan 16;14(1):e0210132. doi: 10.1371/journal.pone.0210132. eCollection 2019.

Authors

James G Bedford¹, Meredith O'Keeffe², Patrick C Reading^{1

3}, Linda M Wakim¹

Affiliations

¹ Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
² Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.
³ WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

Abstract

Interferon-induced transmembrane protein 3 (IFITM3) is a potent antiviral protein that enhances cellular resistance to a variety of pathogens, including influenza virus. Classically defined as an interferon-stimulated gene, expression of IFITM3 on cells is rapidly up-regulated in response to type I and II interferon. Here we found that IFITM3 is rapidly up-regulated by T cells following their activation and this occurred independently of type I and II interferon and the interferon regulatory factors 3 and 7. Up-regulation of IFITM3 on effector T cells protected these cells from virus infection and imparted a survival advantage at sites of virus infection. Our results show that IFITM3 expression on effector T cells is crucial for these cells to mediate their effector function and highlights an interferon independent pathway for the induction of IFITM3 which, if targeted, could be an effective approach to harness the activity of IFITM3 for infection prevention.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adoptive Transfer / methods
Animals
Cells, Cultured
Disease Models, Animal
Dogs
Humans
Influenza A Virus, H1N1 Subtype / immunology
Influenza A Virus, H1N1 Subtype / pathogenicity
Influenza A Virus, H3N2 Subtype / immunology
Influenza A Virus, H3N2 Subtype / pathogenicity
Influenza, Human / immunology*
Influenza, Human / virology
Interferon Regulatory Factor-3 / genetics
Interferon Regulatory Factor-7 / genetics
Interferons / metabolism
Lymphocyte Activation / immunology*
Madin Darby Canine Kidney Cells
Membrane Proteins / genetics
Membrane Proteins / immunology*
Membrane Proteins / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Primary Cell Culture
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism
T-Lymphocytes / transplantation

Substances

Interferon Regulatory Factor-3
Interferon Regulatory Factor-7
Irf3 protein, mouse
Irf7 protein, mouse
Membrane Proteins
fragilis protein, mouse
Interferons

Grants and funding

This work was supported by National Health and Medical Research Council (NHMRC) of Australia and the Australian Research Council (ARC) (LMW). The Melbourne World Health Organization Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health (PR).