Major vault protein directly enhances adaptive immunity induced by Influenza A virus or indirectly through innate immunity

• Published in: Biochimica et biophysica acta. Molecular basis of disease Vol. 1870; no. 7; p. 167441
• Main Authors: Ma, Caijiao, Luo, Chuanjin, Deng, Feiyan, Yu, Chen, Chen, Yumeng, Zhong, Gechang, Zhan, Yuxin, Nie, Longyu, Huang, Yu, Xia, Yongfang, Cai, Zeng, Xu, Ke, Cai, Huanhuan, Wang, Fubing, Lu, Zhibing, Zeng, Xiangtai, Zhu, Ying, Liu, Shi
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2024
• Subjects: Antibody; B cells; Dendritic cells; Influenza a virus; Major vault protein; T cells; Major vault protein; Influenza a virus; B cells; Dendritic cells; T cells; Antibody
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2024.167441

As we previously revealed, major vault protein (MVP) is a virus-induced host factor, and its expression is crucial for innate immune responses. Nevertheless, the function of MVP in adaptive immunity is poorly known. Here, we demonstrate that Mvp knockout mice had attenuated antibody responses and reduced survival after rechallenge with homologous influenza A virus (IAV) relative to wild-type mice. Analysis of B cell populations showed that MVP promoted germinal center (GC) responses to develop optimal antiviral humoral immunity. Although MVP-deficient T cells and dendritic cells (DCs) were not intrinsically damaged, MVP promoted activating effector T cells and T follicular helper responses and regulated specific DC subsets. These findings suggest that MVP directs an effective adaptive immune response against IAV by directly engaging in GC reactions or indirectly augmenting cellular immunity via innate immune pathways. [Display omitted] •MVP protects mice against rechallenge by homologous IAV strains.•MVP enhances IAV-induced antibody responses.•MVP is required for the proliferation and differentiation of B cell subpopulations.•MVP promotes specific T cell responses and Tfh responses.•MVP regulates the kinetics of DC subsets.