Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/26204
Title: Influenza A virus infection-induced macroautophagy facilitates MHC class II-restricted endogenous presentation of an immunodominant viral epitope.
Austin Authors: Deng, Jieru;Lu, Chunni;Liu, Chuanxin;Oveissi, Sara;Fairlie, Walter Douglas ;Lee, Erinna F;Bilsel, Pamuk;Puthalakath, Hamsa;Chen, Weisan
Affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Vic., Australia
School of Cancer Medicine, La Trobe University, Melbourne, Vic., Australia
Olivia Newton-John Cancer Research Institute
School of Medicine, Deakin University, Waurn Ponds, Vic., Australia
FluGen Inc., Madison, WI, USA
Issue Date: May-2021
Date: 2020-12-05
Publication information: The FEBS Journal 2021; 288(10): 3164-3185
Abstract: CD4+ T cells recognize peptides presented by major histocompatibility complex class II molecules (MHC-II). These peptides are generally derived from exogenous antigens. Macroautophagy has been reported to promote endogenous antigen presentation in viral infections. However, whether influenza A virus (IAV) infection-induced macroautophagy also leads to endogenous antigen presentation through MHC-II is still debated. In this study, we show that IAV infection leads to endogenous presentation of an immunodominant viral epitope NP311-325 by MHC-II to CD4+ T cells. Mechanistically, such MHC-II-restricted endogenous IAV antigen presentation requires de novo protein synthesis as it is inhibited by the protein synthesis inhibitor cycloheximide, and a functional ER-Golgi network as it is totally blocked by Brefeldin A. These results indicate that MHC-II-restricted endogenous IAV antigen presentation is dependent on de novo antigen and/or MHC-II synthesis, and transportation through the ER-Golgi network. Furthermore, such endogenous IAV antigen presentation by MHC-II is enhanced by TAP deficiency, indicating some antigenic peptides are of cytosolic origin. Most importantly, the bulk of such MHC-II-restricted endogenous IAV antigen presentation is blocked by autophagy inhibitors (3-MA and E64d) and deletion of autophagy-related genes, such as Beclin1 and Atg7. We have further demonstrated that in dendritic cells, IAV infection prevents autophagosome-lysosome fusion and promotes autophagosome fusion with MHC class II compartment (MIIC), which likely promotes endogenous IAV antigen presentation by MHC-II. Our results provide strong evidence that IAV infection-induced autophagosome formation facilitates endogenous IAV antigen presentation by MHC-II to CD4+ T cells. The implication for influenza vaccine design is discussed.
URI: https://ahro.austin.org.au/austinjspui/handle/1/26204
DOI: 10.1111/febs.15654
ORCID: 0000-0001-5178-1175
0000-0002-5221-9771
Journal: The FEBS Journal
PubMed URL: 33830641
Type: Journal Article
Subjects: CD4+ T cell
MHC‐II
antigen presentation
influenza A virus
macroautophagy
Appears in Collections:Journal articles

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