Dataset Information

B cell immunity to the Lassa virus glycoprotein is a correlate of vaccination-induced viral load control

ABSTRACT: Lassa fever, a viral hemorrhagic fever caused by the arenavirus Lassa virus (LASV), affects thousands of individuals annually, highlighting the need for a vaccine. Yet, immunological correlates of viral load control remain poorly defined. Studying vaccination-induced immunity in a surrogate LASV challenge model we found that LASV-cross-reactive B cell immunity induced by the glycoprotein of distantly related arenaviruses, such as lymphocytic choriomeningitis virus (LCMV), provided significant viral load control in mice. Counter to common concepts, suppression of viremia was observed in the absence of CD8 T cells or neutralizing antibodies but correlated with non-neutralizing glycoprotein-specific antibody responses. Adoptive cell transfer experiments with monoclonal LCMV-specific B cells demonstrated that these cells suppressed viral loads when previously activated by a heterologous cross-reactive glycoprotein and diversified by somatic hypermutation. These findings establish vaccination-induced B cell immunity to the LASV glycoprotein as a correlate of viral load control, independently of virus-neutralizing antibody titers at the time of challenge.

ORGANISM(S): Mus musculus

PROVIDER: GSE313953 | GEO | 2026/02/26

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Lassa fever virus (LASV) is a significant human pathogen that is endemic to several countries in West Africa. Infection with Lassa leads to the development of hemorrhagic fever in a significant number of public health cases and it is considered a potential bioweapon. Little is known about the complex immune mechanisms governing response to LASV infection, or the genetic determinants of susceptibility and resistance to infection. In the study presented here, we have used a whole-genome, microarray-based approach to determine the temporal host response to infection in the peripheral blood mononuclear cells of non-human primates (NHP) infected with LASV. Sequential sampling over the entire disease course showed that there are specific transcription signatures of the immune response to LASV infection, including the rapid up- regulation of interferon-responsive genes and toll-like receptor signaling pathways. However, this increase in early innate responses was coupled with a lack of pro- inflammatory cytokine response in LASV infected NHPs. There was a distinct lack of cytokines such as IL1b and IL23a, while immune suppressive cytokines such as IL27 and IL6 were upregulated. Comparison of cytokine gene expression with the amount of detectable protein in Lassa infected NHPs suggests that gene expression precedes the protein detection and thus is possibly a better tool for early diagnostics of the disease. Our results provide a comprehensive picture of the immune response to hemorrhagic LASV infection and provide a foundation for biomarker identification to allow clinical diagnosis of Lassa infection through analysis of the host response. RNA was isolated from a total of 46 PBMC samples from 15 cynomologus macaques infected with Lassa Virus. Samples were obtained at sequential timepoints post-infection, and included a pre-infection specimen from each animal. A subset of 30 samples (11 animals) were then processed and hybridized onto the Agilent 2-color arrays.

Project description:Rhesus macaques (Macaca mulatta) infected with a lethal dose of lymphocytic choriomeningitis virus-strain WE (LCMV-WE) provide a model for Lassa fever virus infection of man. Like Lassa fever in human beings, disease begins with flu-like symptoms but can progress to morbidity fairly rapidly. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al. J. Virol. 2007: PMID 17522210) showing distinct pre-viremic and viremic stages that discriminated between virulent and benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased. We observed gene expression changes that occurred before the viremic stage of the disease, and could potentially serve as biomarkers that discriminate between exposure to a hemorrhagic fever virus and exposure to a benign virus. Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a much broader effect on liver cell function than non-virulent virus. During the first few days of infection, virulent virus impacted gene expression associated with the generation of energy, such as fatty acid metabolism and glucose metabolism, with the complement and coagulation cascades, and with steroid metabolism, MAPK signaling and cell adhesion. For example, the energy profile resembled that of an organism entering starvation: acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis, was shut down and gene products involved in gluconeogenesis were up-regulated. In conclusion, this study identifies several potential gene markers of LCMV-WE-associated liver disease and contributes to the database of gene expression changes correlated with LCMV pathogenesis in primates. 6 groups: uninfected controls, LCMV-WE infected (pre-viremic; day 1 to day 3), LCMV-WE infected (viremic; day 4 to day 7), LCMV-WE infected (post-viremic; day 8 to day 12), LCMV-Armstrong (LCMV-ARM; non-virulent strain) infected, and LCMV-ARM/LCMV-WE infected but not diseased. Each sample is from the liver of a different rhesus macaque.

Dataset Information

B cell immunity to the Lassa virus glycoprotein is a correlate of vaccination-induced viral load control

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets