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The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81

A single-nucleotide polymorphism (SNP) rs12252-C of interferon-induced transmembrane protein 3 (IFITM3), resulting in a truncated IFITM3 protein lacking 21 N-terminus amino acids, is associated with severe influenza infection in the Chinese population. However, the effect of IFITM3 rs12252-C on infl...

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Autores principales: Xie, Qian, Liao, Xinzhong, Huang, Bi, Wang, Liangliang, Liao, Guancheng, Luo, Chuming, Wen, Simin, Fang, Shisong, Luo, Huanle, Shu, Yuelong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484049/
https://www.ncbi.nlm.nih.gov/pubmed/37556756
http://dx.doi.org/10.1080/22221751.2023.2246599
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author Xie, Qian
Liao, Xinzhong
Huang, Bi
Wang, Liangliang
Liao, Guancheng
Luo, Chuming
Wen, Simin
Fang, Shisong
Luo, Huanle
Shu, Yuelong
author_facet Xie, Qian
Liao, Xinzhong
Huang, Bi
Wang, Liangliang
Liao, Guancheng
Luo, Chuming
Wen, Simin
Fang, Shisong
Luo, Huanle
Shu, Yuelong
author_sort Xie, Qian
collection PubMed
description A single-nucleotide polymorphism (SNP) rs12252-C of interferon-induced transmembrane protein 3 (IFITM3), resulting in a truncated IFITM3 protein lacking 21 N-terminus amino acids, is associated with severe influenza infection in the Chinese population. However, the effect of IFITM3 rs12252-C on influenza vaccination and the underlying mechanism is poorly understood. Here, we constructed a mouse model with a deletion of 21 amino acids at the N-terminus (NΔ21) of IFITM3 and then compared the antibody response between Quadrivalent influenza vaccine (QIV) immunized wild-type (WT) mice and NΔ21 mice. Significantly higher levels of haemagglutination inhibition (HI) titre, neutralizing antibodies (NAb), and immunoglobulin G (IgG) to H1N1, H3N2, B/Victory, and B/Yamagata viruses were observed in NΔ21 mice compared to WT mice. Correspondingly, the numbers of splenic germinal centre (GC) B cells, plasma cells, memory B cells, QIV-specific IgG(+) antibody-secreting cells (ASC), and T follicular helper cells (T(FH)) in NΔ21 mice were higher compared with WT mice. Moreover, the 21-amino-acid deletion caused IFITM3 translocation from the endocytosis compartment to the periphery of cells, which also prevented the degradation of a co-stimulatory molecule of B cell receptor (BCR) CD81 on the cell surface. More importantly, a more interaction was observed between NΔ21 protein and CD81 compared to the interaction between IFITM3 and CD81. Overall, our study revealed a potential mechanism of NΔ21 protein enhancing humoral immune response by relocation to prevent the degradation of CD81, providing insight into SNP affecting influenza vaccination.
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spelling pubmed-104840492023-09-08 The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81 Xie, Qian Liao, Xinzhong Huang, Bi Wang, Liangliang Liao, Guancheng Luo, Chuming Wen, Simin Fang, Shisong Luo, Huanle Shu, Yuelong Emerg Microbes Infect Influenza Infections A single-nucleotide polymorphism (SNP) rs12252-C of interferon-induced transmembrane protein 3 (IFITM3), resulting in a truncated IFITM3 protein lacking 21 N-terminus amino acids, is associated with severe influenza infection in the Chinese population. However, the effect of IFITM3 rs12252-C on influenza vaccination and the underlying mechanism is poorly understood. Here, we constructed a mouse model with a deletion of 21 amino acids at the N-terminus (NΔ21) of IFITM3 and then compared the antibody response between Quadrivalent influenza vaccine (QIV) immunized wild-type (WT) mice and NΔ21 mice. Significantly higher levels of haemagglutination inhibition (HI) titre, neutralizing antibodies (NAb), and immunoglobulin G (IgG) to H1N1, H3N2, B/Victory, and B/Yamagata viruses were observed in NΔ21 mice compared to WT mice. Correspondingly, the numbers of splenic germinal centre (GC) B cells, plasma cells, memory B cells, QIV-specific IgG(+) antibody-secreting cells (ASC), and T follicular helper cells (T(FH)) in NΔ21 mice were higher compared with WT mice. Moreover, the 21-amino-acid deletion caused IFITM3 translocation from the endocytosis compartment to the periphery of cells, which also prevented the degradation of a co-stimulatory molecule of B cell receptor (BCR) CD81 on the cell surface. More importantly, a more interaction was observed between NΔ21 protein and CD81 compared to the interaction between IFITM3 and CD81. Overall, our study revealed a potential mechanism of NΔ21 protein enhancing humoral immune response by relocation to prevent the degradation of CD81, providing insight into SNP affecting influenza vaccination. Taylor & Francis 2023-09-06 /pmc/articles/PMC10484049/ /pubmed/37556756 http://dx.doi.org/10.1080/22221751.2023.2246599 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Influenza Infections
Xie, Qian
Liao, Xinzhong
Huang, Bi
Wang, Liangliang
Liao, Guancheng
Luo, Chuming
Wen, Simin
Fang, Shisong
Luo, Huanle
Shu, Yuelong
The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81
title The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81
title_full The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81
title_fullStr The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81
title_full_unstemmed The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81
title_short The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81
title_sort truncated ifitm3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with cd81
topic Influenza Infections
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484049/
https://www.ncbi.nlm.nih.gov/pubmed/37556756
http://dx.doi.org/10.1080/22221751.2023.2246599
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