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

James G. Bedford,Linda M. Wakim,Meredith O’Keeffe,Patrick C. Reading,Dong-Yan Jin

doi:10.1371/journal.pone.0210132

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.

Highlights

Cells are equipped with a variety of mechanisms to protect themselves from virus infection
We have previously reported that dendritic cells stationed within the lung upregulate Interferon-induced transmembrane 3 (IFITM3) following influenza virus infection, a process driven by exposure to type I interferon, and this was crucial for these cells to successfully traffic influenza viral antigen from the lung to draining lymph node (LN) without becoming infected and perishing en route [23]
We find that IFITM3 is rapidly up-regulated on T cells following their activation in the draining LN and expression is maintained as these cells infiltrate sites of virus infection

Summary

Introduction

Cells are equipped with a variety of mechanisms to protect themselves from virus infection. Following in vitro activation of these cells (as described above) we observed upregulation of IFITM3 expression, albeit less effectively (Fig 1E and 1F) indicating that the induction of IFITM3 expression by engagement of the TCR was, at least in part, independent of type I and II interferon signalling.

Results

Conclusion