Original Research ARTICLE
Downregulation of MHC class I expression by influenza A and B viruses
- 1The University of Melbourne, Australia
- 2Monash University, Australia
- 3Department of Microbiology and Immunology, The University of Melbourne, Australia
Manipulation of the MHC-I presentation pathway, and thus limiting MHC-I cell surface expression, is used by many viruses to evade immune recognition. In particular, downregulation of MHC-I molecules at the cell surface can reduce the ability of CD8+ T cells to recognise viral peptides presented by MHC-I molecules and thereby delay viral clearance by CD8+ T cells. To date, MHC-I downregulation by influenza viruses has not been reported. Given that influenza virus infections are a global health concern and that CD8+ T cells play an important role in promoting influenza virus clearance and recovery from influenza disease, we investigated whether influenza A and B viruses (IAV, IBV) downregulated MHC-I as a novel mechanism to evade cellular immunity. Here, we showed that infection of several cell types, including epithelial A549 cells, with a panel of IAV and IBV viruses downregulated the surface MHC-I expression on IAV/IBV-infected cells during the late stages of influenza virus infection. This observation was consistent across a panel of class I-reduced (C1R) cell lines expressing 14 different HLA-A or -B alleles and a panel of 721.221 cell lines expressing 11 HLA-C alleles. Interestingly, IBV infection caused more pronounced reduction in surface MHC-I expression compared to IAV. Importantly, the two viruses utilized two distinct mechanisms for MHC-I downregulation. Our data demonstrated that while IAV caused a global loss of MHC-I within influenza-infected cells, IBV infection resulted in the preferential loss of MHC-I molecules from the cell surface, consequent of delayed MHC-I trafficking to the cell surface, resulting from retaining MHC-I intracellularly during IBV infection. Overall, our study suggests that influenza viruses across both IAV and IBV subtypes have the potential to downregulate MHC-I surface expression levels. Our findings provide new insights into the host-pathogen interaction of influenza A and B viruses and inform the design of novel vaccine strategies against influenza viruses.
Keywords: Influenza A virus, Influenza B virus, MHC-I, HLA, T cells
Received: 20 Nov 2018;
Accepted: 08 May 2019.
Edited by:Abhijeet A. Bakre, University of Georgia, United States
Reviewed by:Marina Cella, Washington University School of Medicine in St. Louis, United States
Marco De Giovanni, San Raffaele Scientific Institute (IRCCS), Italy
Copyright: © 2019 Koutsakos, McWilliam, Aktepe, Fritzlar, Illing, Mifsud, Purcell, Rockman, READING, Vivian, Rossjohn, Brooks, Mackenzie, Mintern, Villadangos, Kedzierska and Nguyen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Katherine Kedzierska, The University of Melbourne, Department of Microbiology and Immunology, Melbourne, Australia, firstname.lastname@example.org