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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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2246599 |
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| author | Qian Xie Xinzhong Liao Bi Huang Liangliang Wang Guancheng Liao Chuming Luo Simin Wen Shisong Fang Huanle Luo Yuelong Shu |
| author_facet | Qian Xie Xinzhong Liao Bi Huang Liangliang Wang Guancheng Liao Chuming Luo Simin Wen Shisong Fang Huanle Luo Yuelong Shu |
| author_sort | Qian Xie |
| collection | DOAJ |
| 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 (TFH) 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. |
| format | Article |
| id | doaj-art-1ee653f124434e5d801f4f3df875f272 |
| institution | DOAJ |
| issn | 2222-1751 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-1ee653f124434e5d801f4f3df875f2722025-08-20T03:14:59ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2246599The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81Qian Xie0Xinzhong Liao1Bi Huang2Liangliang Wang3Guancheng Liao4Chuming Luo5Simin Wen6Shisong Fang7Huanle Luo8Yuelong Shu9School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaGuangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, People’s Republic of ChinaPathogenic Microorganism Testing Institute, Shenzhen Center for Disease Control and Prevention, Shenzhen, People’s Republic of ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaA 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 (TFH) 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.https://www.tandfonline.com/doi/10.1080/22221751.2023.2246599IFITM3influenza virusIFITM3 rs12252vaccination |
| spellingShingle | Qian Xie Xinzhong Liao Bi Huang Liangliang Wang Guancheng Liao Chuming Luo Simin Wen Shisong Fang Huanle Luo Yuelong Shu The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81 Emerging Microbes and Infections IFITM3 influenza virus IFITM3 rs12252 vaccination |
| 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 | IFITM3 influenza virus IFITM3 rs12252 vaccination |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2246599 |
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