Downregulation of MHC class I expression by influenza A and B viruses

Journal article


Koutsakos, Marios, McWilliam, Hamish E.G., Aktepe, Turgut E., Fritzlar, Svenja, Illing, Patricia T., Mifsud, Nicole A., Purcell, Anthony W., Rockman, Steve, Reading, Patrick C., Vivian, Julian P., Rossjohn, Jamie, Brooks, Andrew G., Mackenzie, Jason M., Mintern, Justine D., Villadangos, Jose A., Nguyen, Thi H. O. and Kedzierska, Katherine. (2019). Downregulation of MHC class I expression by influenza A and B viruses. Frontiers in Immunology. 10, p. Article 1158. https://doi.org/10.3389/fimmu.2019.01158
AuthorsKoutsakos, Marios, McWilliam, Hamish E.G., Aktepe, Turgut E., Fritzlar, Svenja, Illing, Patricia T., Mifsud, Nicole A., Purcell, Anthony W., Rockman, Steve, Reading, Patrick C., Vivian, Julian P., Rossjohn, Jamie, Brooks, Andrew G., Mackenzie, Jason M., Mintern, Justine D., Villadangos, Jose A., Nguyen, Thi H. O. and Kedzierska, Katherine
Abstract

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 recognize 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 in vitro. 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.

Keywordsinfluenza A virus; influenza B virus; MHC-I; HLA; T cells
Year2019
JournalFrontiers in Immunology
Journal citation10, p. Article 1158
PublisherFrontiers Media S.A.
ISSN1664-3224
Digital Object Identifier (DOI)https://doi.org/10.3389/fimmu.2019.01158
PubMed ID31191533
Scopus EID2-s2.0-85068149127
PubMed Central IDPMC6548845
Open accessPublished as ‘gold’ (paid) open access
Page range1-12
FunderNational Health and Medical Research Council (NHMRC)
University of Melbourne
Department of Health, Australian Government
Australian Research Council (ARC)
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online29 May 2019
Publication process dates
Accepted08 May 2019
Deposited28 Nov 2023
ARC Funded ResearchThis output has been funded, wholly or partially, under the Australian Research Council Act 2001
Grant ID1071916
DE170100575
1163090
170102471
1085018
1137739
1072159
Permalink -

https://acuresearchbank.acu.edu.au/item/8zzv2/downregulation-of-mhc-class-i-expression-by-influenza-a-and-b-viruses

Download files


Publisher's version
  • 51
    total views
  • 14
    total downloads
  • 3
    views this month
  • 1
    downloads this month
These values are for the period from 19th October 2020, when this repository was created.

Export as

Related outputs

Engineering Cell Lines for Specific Human Leukocyte Antigen Presentation
Jin, Dongbin, Loh, Khai Lee, Shamekhi, Tima, Ting, Yi Tian, Lim Kam Sian, Terry C. C., Roest, James, Ooi, Joshua D., Vivian, Julian Philip and Faridi, Pouya. (2023). Engineering Cell Lines for Specific Human Leukocyte Antigen Presentation. In In Jenkins, Brendan J. (Ed.). Inflammation and Cancer : Methods and Protocols pp. 351-369 Springer - Humana Press. https://doi.org/10.1007/978-1-0716-3331-1_25
Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection
Ullah, Tomalika R., Johansen, Matt D., Balka, Katherine R., Ambrose, Rebecca L., Gearing, Linden J., Roest, James, Vivian, Julian Philip, Sapkota, Sunil, Jayasekara, W. Samantha N., Wenholz, Daniel S., Aldilla, Vina R., Zeng, Jun, Miemczyk, Stefan, Nguyen, Duc H. and et. al.. (2023). Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection. Nature Communications. 14(1), pp. 1-13. https://doi.org/10.1038/s41467-023-41381-9
Characterization of Monoclonal Antibodies to Measure Cell Surface Protein Levels of Human Interferon-Lambda Receptor 1
de Weerd, Nicole A., Ogungbola, Olamide, Liu, Xinyun, Matthews, Antony Y., Ismail, Amina, Vivian, Julian Philip, Lim, San S., Tyrrell, D. Lorne, Putcha, Niru, Skawinski, Mike, Dickensheets, Harold, Lavoie, Thomas B., Donnelly, Raymond P., Hertzog, Paul J. and Santer, Deanna M.. (2023). Characterization of Monoclonal Antibodies to Measure Cell Surface Protein Levels of Human Interferon-Lambda Receptor 1. Journal of Interferon and Cytokine Research. 43(9), pp. 403-413. https://doi.org/10.1089/jir.2023.0040
Polymorphic KIR3DL3 expression modulates tissue-resident and innate-like T cells
Palmer, William H., Leaton, Laura Ann, Codo, Ana Campos, Crute, Bergren, Roest, James, Zhu, Shiying, Petersen, Jan, Tobin, Richard P., Hume, Patrick S., Stone, Matthew, van Bokhoven, Adrie, Gerich, Mark E., McCarter, Martin D., Zhu, Yuwen, Janssen, William J., Vivian, Julian Philip, Trowsdale, John, Getahun, Andrew, Rossjohn, Jamie, ... Norman, Paul J.. (2023). Polymorphic KIR3DL3 expression modulates tissue-resident and innate-like T cells. Science Immunology. 8(84), pp. 1-18. https://doi.org/10.1126/sciimmunol.ade5343
The allopurinol metabolite, oxypurinol, drives oligoclonal expansions of drug-reactive T cells in resolved hypersensitivity cases and drug-naïve healthy donors
Mifsud, Nicole A., Illing, Patricia T., Ho, Rebecca, Tuomisto, Johanna E., Fettke, Heidi, Mullan, Kerry A., McCluskey, James, Rossjohn, Jamie, Vivian, Julian Philip, Reantragoon, Rangsima and Purcell, Anthony W.. (2023). The allopurinol metabolite, oxypurinol, drives oligoclonal expansions of drug-reactive T cells in resolved hypersensitivity cases and drug-naïve healthy donors. Allergy. 78(11), pp. 2980-2993. https://doi.org/10.1111/all.15814
Structural plasticity of KIR2DL2 and KIR2DL3 enables altered docking geometries atop HLA-C
Moradi, Shoeib, Stankovic, Sanda, O’Connor, Geraldine M., Pymm, Phillip, MacLachlan, Bruce J., Faoro, Camilla, Retière, Christelle, Sullivan, Lucy C., Saunders, Philippa M., Widjaja, Jacqueline, Cox-Livingstone, Shea, Rossjohn, Jamie, Brooks, Andrew G. and Vivian, Julian P.. (2021). Structural plasticity of KIR2DL2 and KIR2DL3 enables altered docking geometries atop HLA-C. Nature Communications. 12(1), p. Article 2173. https://doi.org/10.1038/s41467-021-22359-x
Growth hormone stops excessive inflammation after partial hepatectomy, allowing liver regeneration and survival through induction of H2-Bl/HLA-G
Ishikawa, Mayumi, Brooks, Andrew J., Fernández-Rojo, Manuel A., Medina, Johan, Chhabra, Yash, Minami, Shiro, Tunny, Kathryn A., Parton, Robert G., Vivian, Julian Philip, Rossjohn, Jamie, Chikani, Viral, Ramm, Grant A., Ho, Ken K.Y. and Waters, Michael J.. (2021). Growth hormone stops excessive inflammation after partial hepatectomy, allowing liver regeneration and survival through induction of H2-Bl/HLA-G. Hepatology. 73(2), pp. 759-775. https://doi.org/10.1002/hep.31297
The role of the HLA Class I α2 Helix in determining ligand hierarchy for the killer cell Ig-like Receptor 3DL1
Saunders, Philippa M., MacLachlan, Bruce J., Widjaja, Jacqueline, Wong, Shu Cheng, Oates, Clare V. L., Rossjohn, Jamie, Vivian, Julian P. and Brooks, Andrew G.. (2021). The role of the HLA Class I α2 Helix in determining ligand hierarchy for the killer cell Ig-like Receptor 3DL1. Journal of Immunology. 206(4), pp. 849-860. https://doi.org/10.4049/jimmunol.2001109
Carbamazepine induces focused T cell responses in resolved Stevens-Johnson syndrome and toxic epidermal necrolysis cases but does not perturb the immunopeptidome for T cell recognition
Mifsud, Nicole A., Illing, Patricia T., Lai, Jeffrey W., Fettke, Heidi, Hensen, Luca, Huang, Ziyi, Rossjohn, Jamie, Vivian, Julian Philip, Kwan, Patrick and Purcell, Anthony W.. (2021). Carbamazepine induces focused T cell responses in resolved Stevens-Johnson syndrome and toxic epidermal necrolysis cases but does not perturb the immunopeptidome for T cell recognition. Frontiers in Immunology. 12, p. Article 653710. https://doi.org/10.3389/fimmu.2021.653710
Structural integrity with functional plasticity : What type I IFN receptor polymorphisms reveal
de Weerd, Nicole A., Vivian, Julian P., Lim, San S., Huang, Stephanie U-Shane and Hertzog, Paul J.. (2020). Structural integrity with functional plasticity : What type I IFN receptor polymorphisms reveal. Journal of Leukocyte Biology. 108(3), pp. 909-924. https://doi.org/10.1002/JLB.2MR0420-152R
The molecular basis of how buried human leukocyte antigen polymorphism modulates natural killer cell function
Saunders, Philippa M., MacLachlan, Bruce J., Pymm, Phillip, Illing, Patricia T., Deng, Yuanchen, Wong, Shu Cheng, Oates, Clare V. L., Purcell, Anthony W., Rossjohn, Jamie, Vivian, Julian P. and Brooks, Andrew G.. (2020). The molecular basis of how buried human leukocyte antigen polymorphism modulates natural killer cell function. Proceedings of the National Academy of Sciences of the United States of America. 117(21), pp. 11636-11647. https://doi.org/10.1073/pnas.1920570117
Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1
Martin, Maureen P., Naranbhai, Vivek, Shea, Patrick R., Qi, Ying, Ramsuran, Veron, Vince, Nicolas, Gao, Xiaojiang, Thomas, Rasmi, Brumme, Zabrina L., Carlson, Jonathan M., Wolinsky, Steven M., Goedert, James J., Walker, Bruce D., Segal, Florencia P., Deeks, Steven G., Haas, David W., Migueles, Stephen A., Connors, Mark, Michael, Nelson, ... Carrington, Mary. (2018). Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1. Journal of Clinical Investigation. 128(5), pp. 1903-1912. https://doi.org/10.1172/JCI98463
HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome
Illing, Patricia T., Pymm, Phillip, Croft, Nathan P., Hilton, Hugo G., Jojic, Vladimir, Han, Alex S., Mendoza, Juan L., Mifsud, Nicole A., Dudek, Nadine L., McCluskey, James, Parham, Peter, Rossjohn, Jamie, Vivian, Julian P. and Purcell, Anthony W.. (2018). HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome. Nature Communications. 9(1), p. Article 4693. https://doi.org/10.1038/s41467-018-07109-w
A subset of HLA-I peptides are not genomically templated : Evidence for cis- and trans-spliced peptide ligands
Faridi, Pouya, Li, Chen, Ramarathinam, Sri H., Vivian, Julian P., Illing, Patricia T., Mifsud, Nicole A., Ayala, Rochelle, Song, Jiangning, Gearing, Linden J., Hertzog, Paul J., Ternette, Nicola, Rossjohn, Jamie, Croft, Nathan P. and Purcell, Anthony W.. (2018). A subset of HLA-I peptides are not genomically templated : Evidence for cis- and trans-spliced peptide ligands. Science Immunology. 3(28), p. Article eaar3947. https://doi.org/10.1126/sciimmunol.aar3947