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Overexpression of GitrL in Recombinant Rabies Virus rLBNSE-GitrL Enhances Innate Immunity by Activating Dendritic Cells and Innate Immune-Related Pathways and Genes

Year: 2025
Type: article
Abstract: Rabies, a zoonotic infectious disease causing central nervous system inflammation, remains a threat to public health in regions with limited medical resources. Vaccination effectively reduces rabies incidence and mortality, underscoring the need for vaccines that are cost-effective, immunogenic, protective, and safe. This study constructed a recombinant rabies virus (rRABV)-overexpressing glucocorticoid-induced tumor necrosis factor receptor ligand (GitrL), named rLBNSE-GitrL, using a reverse genetic operating system. rLBNSE-GitrL exhibited similar in vitro phenotypic characteristics and immune safety as the parent RABV (rLBNSE). This recombinant virus stimulated the production of a greater number of activated dendritic cells (DCs) compared to rLBNSE. The enhanced innate immune response induced by rLBNSE-GitrL may be mediated through the activation of innate immune-related signaling pathways, such as the tumor necrosis factor (TNF), and chemokine signaling pathways, and the upregulation of a series of innate immune-related genes, including MMP2, IL-6, CXCL9, TIMP1, IL-17d, and TNF-α. Consequently, rLBNSE-GitrL elicited significantly higher levels of RABV vaccine-induced virus-neutralizing antibodies (VNA), IgG, and IgM compared to rLBNSE as early as 3 days post-immunization (dpi), thereby improving the protective effect in mice. Collectively, the overexpression of GitrL facilitated the induction of early and potent antibody responses following RABV immunization.
Source: Viruses
DOI: 10.3390/v17101354
Authors: Yufang Wang, Xiao Xing, Zhimin Xiong, Yong Wang, Yaping Liu, Yingying Li
Language: English
Subfield: Virology
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W4415008593
FWCI: 0.453
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Cited by: 1
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