GEO series

Yellow fever vaccine propagation in primary human hepatocytes triggers antiviral and cytolytic responses

GSE306280 Homo sapiens (human) RNA-seq (gene expression) 36 samples Submitted 2025/08/26 Platform GPL30173

At a glance

RNA-seq (gene expression) · human · 36 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 36 samples: 36 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Despite the long-standing success of the yellow fever virus (YFV) 17D vaccine, the precise virus and host determinants which confer its virulence attenuation remain incompletely defined. To provide insights, we performed YFV genome-level evolutionary analyses combined with investigations of vaccine hepatotropism. Evolutionary analyses confirmed vaccine-specific mutations are selected against in virulent YFV isolates, with genomic signatures of purifying selection most pronounced in the envelope (E) protein, where vaccine-specific mutations are concentrated.

Read the full summary ↓

Structural prediction and mapping using Alphafold3 confirmed vaccine-specific mutations form a surface-exposed patch on domain III of the E protein, likely overlapping the flavivirus receptor binding domain. In tissue culture, 17D infections exhibited enhanced cell-to-cell spread and cytolysis compared to virulent YFV strains. In humans, YFV infections cause severe liver damage while vaccination has an excellent safety profile. Consequently, we next investigated whether 17D displays impaired tropism for primary human hepatocytes (PHH) or induces distinct cell-intrinsic responses to virulent strains. Surprisingly, ex vivo infections confirmed robust propagation of both 17D and virulent YFV strains in PHH. RNA-sequencing revealed consistent and shared induction of IFNB and IFNL1-4, modulating gene programs associated with antiviral responses, cellular immunity, chemotaxis and inflammation, cell-death, metabolism and protein translation. Consistent with differences in spreading efficiency, subtle differences in virion production kinetics and the magnitude and tempo of PHH transcriptional responses were observed. Antiviral responses to 17D were activated earlier while responses to virulent YFV were delayed but enhanced. In summary, we confirm the YFV vaccine exhibits comparable hepatotropism to virulent strains and induces virtually identical host responses. Mechanistically, these data suggest that impaired hepatotropism and associated cytopathology are not correlates of 17D’s virulence attenuation, implying unknown barriers to systemic dissemination mitigate viscerotropic spread and associated liver pathology upon vaccination.

This dataset

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Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE306280_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1310406 and SRA study SRP612588. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

36 samples, each with a distinct title — no replicated groups

Supports a case/control comparison: 27 samples read as cases, 9 as controls.

How we read this: Read from 36 sample titles: 36 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM9196679 24 hpi, Donor 1, mock
GSM9196680 24 hpi, Donor 2, mock
GSM9196681 24 hpi, Donor 3, mock
GSM9196682 24 hpi, Donor 1, 17D infected
GSM9196683 24 hpi, Donor 2, 17D infected
GSM9196684 24 hpi, Donor 3, 17D infected
GSM9196685 24 hpi, Donor 1, Asibi infected
GSM9196686 24 hpi, Donor 2, Asibi infected
GSM9196687 24 hpi, Donor 3, Asibi infected
GSM9196688 24 hpi, Donor 1, Uganda infected
GSM9196689 24 hpi, Donor 2, Uganda infected
GSM9196690 24 hpi, Donor 3, Uganda infected
GSM9196691 48 hpi, Donor 1, mock
GSM9196692 48 hpi, Donor 2, mock
GSM9196693 48 hpi, Donor 3, mock
GSM9196694 48 hpi, Donor 1, 17D infected
GSM9196695 48 hpi, Donor 2, 17D infected
GSM9196696 48 hpi, Donor 3, 17D infected
GSM9196697 48 hpi, Donor 1, Asibi infected
GSM9196698 48 hpi, Donor 2, Asibi infected
GSM9196699 48 hpi, Donor 3, Asibi infected
GSM9196700 48 hpi, Donor 1, Uganda infected
GSM9196701 48 hpi, Donor 2, Uganda infected
GSM9196702 48 hpi, Donor 3, Uganda infected
GSM9196703 72 hpi, Donor 1, mock
GSM9196704 72 hpi, Donor 2, mock
GSM9196705 72 hpi, Donor 3, mock
GSM9196706 72 hpi, Donor 1, 17D infected
GSM9196707 72 hpi, Donor 2, 17D infected
GSM9196708 72 hpi, Donor 3, 17D infected
GSM9196709 72 hpi, Donor 1, Asibi infected
GSM9196710 72 hpi, Donor 2, Asibi infected
GSM9196711 72 hpi, Donor 3, Asibi infected
GSM9196712 72 hpi, Donor 1, Uganda infected
GSM9196713 72 hpi, Donor 2, Uganda infected
GSM9196714 72 hpi, Donor 3, Uganda infected

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.